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Ngamsangiam W, Techa-ay S, Sa-ngiamwibool P, Watcharadetwittaya S, Deenonpoe R, Techasen A, Sridakhun N, Padthaisong S, Thanee M. Distinct chromosome abnormality patterns for differential diagnosis of hepatocellular carcinoma and cholangiocarcinoma. PLoS One 2025; 20:e0322408. [PMID: 40354349 PMCID: PMC12068623 DOI: 10.1371/journal.pone.0322408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Accepted: 03/20/2025] [Indexed: 05/14/2025] Open
Abstract
Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) are primary liver cancers with overlapping histopathological features, making accurate diagnosis challenging. This study aimed to identify chromosomal abnormalities that could aid in differentiating these cancers using chromosome microarray analysis (CMA). We analyzed ten frozen tumor tissues each of HCC and CCA, identifying distinct patterns of chromosomal gains and losses. HCC exhibited gains in regions 1p36.32, 1q23.3-q24.1, 3q21.3, 4p16.1, 5q31.1, and 11p15.5, and losses in 2p15, 3p11.1-q11.1, 4q12, 5p12-q11.1, 7q11.23, 14q23.2, 17p11.2, 17p13.3, 22q12.1, 22q12.2-q12.3, and 22q13.2. In contrast, CCA showed gains in 5p13.2, 5p14.1, 8p12-p11.23, 8p22, and 19p13.2, and losses in 1q31.1, 1q42.13, 3p25.3, 6p12.1, 6p25.3, and 17q21.33. Heatmap analysis revealed 17 distinct chromosomal regions between the two groups including 2q14.2, 4p16.3, 5q32, 7p14.3, 7p22.1, 7q11.21, 7q11.23, 7q21.3, 7q22.1, 10q21.3, 18q23, 19p13.2, 19q13.2, 21q21.3, 21q22.13, 22q11.21, and 22q12.2. Among these 1p36.32, 19p13.2, and 19q13.2 emerged as potential biomarkers for differential diagnosis. These findings may aid in confirming cases with overlapping histopathological features contribute to the development of diagnostic tools and improved targeted therapies for HCC and CCA.
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Affiliation(s)
- Wantakan Ngamsangiam
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
| | - Sutheemon Techa-ay
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
| | - Prakasit Sa-ngiamwibool
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
| | - Sasithorn Watcharadetwittaya
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
| | - Raksawan Deenonpoe
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
| | - Anchalee Techasen
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Faculty of Associated Medical Science, Khon Kaen University, Khon Kaen, Thailand
| | - Natruja Sridakhun
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | | | - Malinee Thanee
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
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Wang T, Bao X, Yang F, Pan S, Xu K, Ren T. Plasma COL10A1 Level, a Potential Diagnostic and Prognostic Biomarker for Pancreatic Ductal Adenocarcinoma. Onco Targets Ther 2024; 17:949-959. [PMID: 39525356 PMCID: PMC11550710 DOI: 10.2147/ott.s474540] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Accepted: 11/01/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND COL10A1 expression was up-regulated and could promote tumor development in pancreatic cancer. As a secreted protein, plasma COL10A1 level was proven to have certain diagnostic efficacy in gastric cancer, breast cancer, and colorectal cancer. It is still unknown whether it has a biomarker role for pancreatic cancer. AIM To explore and analyze the diagnostic and prognostic value of plasma COL10A1 level in pancreatic ductal adenocarcinoma (PDAC). METHOD The RNA-seq dataset of PDAC from The Cancer Genome Atlas (TCGA) and six expression profiling microarray datasets from Gene Expression Omnibus (GEO) were downloaded to analyze the expression of COL10A1 in tissues. Thirty-six patients with PDAC and eighteen healthy volunteers were enrolled to measure COL10A1 levels in tissues and plasmas, and the relationship between clinical characteristics and the COL10A1 levels was analyzed. The diagnostic and prognostic efficacy of plasma COL10A1 levels were calculated. RESULTS Aspects of COL10A1 expression level in tissues, COL10A1 expression was significantly higher in PDAC tissue than adjacent normal tissue. The expression of COL10A1 was correlated with T, M, and AJCC stages. Patients with high COL10A1 expression had worse recurrence-free survival (RFS) and overall survival (OS) than those with low expression. Aspects of COL10A1 expression levels in plasma, its diagnostic area under the curve (AUC) for PDAC was 0.926 (95% CI 0.853-0.999), diagnostic sensitivity was 81% (95% CI 64-92%), and specificity was 100% (95% CI 81-100%). The time-dependent AUCs at 1-year and 3-year were 0.71 (95% CI 0.51-0.90) and 0.74 (95% CI 0.48-1.00), respectively. CONCLUSION In PDAC, plasma COL10A1 levels showed certain diagnostic and prognostic efficacy. COL10A1 may be a diagnostic and prognostic biomarker for PDAC and play a role in liquid biopsy of this disease.
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Affiliation(s)
- Tianlei Wang
- Clinical Medical College, Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China
- Department of Oncology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China
| | - Xinrui Bao
- Clinical Medical College, Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China
- Department of Oncology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China
| | - Fang Yang
- Clinical Medical College, Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China
- Department of Oncology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China
| | - Shenbin Pan
- Clinical Medical College, Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China
- Department of Oncology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China
| | - Ke Xu
- Clinical Medical College, Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China
- Department of Oncology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China
| | - Tao Ren
- Clinical Medical College, Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China
- Department of Oncology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China
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Liu D, Li J, Xue Y, Zhao T, Jin Z, Dan W, Chen Z, Hu L, Sun S. Site-specific N-glycan alterations on haptoglobin as potential biomarkers for distinguishing intrahepatic cholangiocarcinoma from hepatocellular carcinoma. Int J Biol Macromol 2024; 280:135563. [PMID: 39284470 DOI: 10.1016/j.ijbiomac.2024.135563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 08/28/2024] [Accepted: 09/09/2024] [Indexed: 09/20/2024]
Abstract
Intrahepatic cholangiocellular carcinoma (ICC) is a challenging malignancy marked by subtle early symptoms and a high mortality rate, making effective diagnostic markers crucial for early detection and improved patient outcomes. Currently, the conventional diagnosis of ICC is not easily distinguishable from Hepatocellular Carcinoma (HCC) and lacks highly specific and sensitive diagnostic markers. Protein glycosylation, pivotal in biological processes, shows promise for cancer biomarkers due to its association with disease progression. This study aims to develop a novel biomarker discovery framework for ICC utilizing site-specific quantitative N-glycoproteomics to overcome the limitations of existing diagnostic approaches. Employing a tandem mass tag (TMT)-based quantitative analysis, we profiled serum glycoproteins from ICC, HCC, and control cohorts at site-specific glycosylation level. The identified markers underwent further validation in an independent cohort using label-free quantitative methods. Ultimately, we identified five site-specific N-glycans on haptoglobin (HP) as potential biomarkers (AUC > 0.9) for distinguishing ICC from HCC. This finding represents a considerable advance over traditional biomarkers, highlighting the significance of protein glycosylation alterations in ICC pathogenesis. This research, therefore, sets a new precedent for biomarker discovery in ICC, with potential applications in other cancers characterized by glycosylation abnormalities.
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Affiliation(s)
- Didi Liu
- Laboratory for Disease Glycoproteomics, College of Life Sciences, Northwest University, Xi'an 710069, PR China
| | - Jun Li
- Laboratory for Disease Glycoproteomics, College of Life Sciences, Northwest University, Xi'an 710069, PR China
| | - Yue Xue
- Laboratory for Disease Glycoproteomics, College of Life Sciences, Northwest University, Xi'an 710069, PR China
| | - Ting Zhao
- Laboratory for Disease Glycoproteomics, College of Life Sciences, Northwest University, Xi'an 710069, PR China
| | - Zhehui Jin
- Laboratory for Disease Glycoproteomics, College of Life Sciences, Northwest University, Xi'an 710069, PR China
| | - Wei Dan
- Laboratory for Disease Glycoproteomics, College of Life Sciences, Northwest University, Xi'an 710069, PR China
| | - Zexuan Chen
- Laboratory for Disease Glycoproteomics, College of Life Sciences, Northwest University, Xi'an 710069, PR China
| | - Liangshuo Hu
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China
| | - Shisheng Sun
- Laboratory for Disease Glycoproteomics, College of Life Sciences, Northwest University, Xi'an 710069, PR China.
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Li B, Kugeratski FG, Kalluri R. A novel machine learning algorithm selects proteome signature to specifically identify cancer exosomes. eLife 2024; 12:RP90390. [PMID: 38529947 PMCID: PMC10965221 DOI: 10.7554/elife.90390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/27/2024] Open
Abstract
Non-invasive early cancer diagnosis remains challenging due to the low sensitivity and specificity of current diagnostic approaches. Exosomes are membrane-bound nanovesicles secreted by all cells that contain DNA, RNA, and proteins that are representative of the parent cells. This property, along with the abundance of exosomes in biological fluids makes them compelling candidates as biomarkers. However, a rapid and flexible exosome-based diagnostic method to distinguish human cancers across cancer types in diverse biological fluids is yet to be defined. Here, we describe a novel machine learning-based computational method to distinguish cancers using a panel of proteins associated with exosomes. Employing datasets of exosome proteins from human cell lines, tissue, plasma, serum, and urine samples from a variety of cancers, we identify Clathrin Heavy Chain (CLTC), Ezrin, (EZR), Talin-1 (TLN1), Adenylyl cyclase-associated protein 1 (CAP1), and Moesin (MSN) as highly abundant universal biomarkers for exosomes and define three panels of pan-cancer exosome proteins that distinguish cancer exosomes from other exosomes and aid in classifying cancer subtypes employing random forest models. All the models using proteins from plasma, serum, or urine-derived exosomes yield AUROC scores higher than 0.91 and demonstrate superior performance compared to Support Vector Machine, K Nearest Neighbor Classifier and Gaussian Naive Bayes. This study provides a reliable protein biomarker signature associated with cancer exosomes with scalable machine learning capability for a sensitive and specific non-invasive method of cancer diagnosis.
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Affiliation(s)
- Bingrui Li
- Department of Cancer Biology, University of Texas MD Anderson Cancer CenterHoustonUnited States
| | - Fernanda G Kugeratski
- Department of Cancer Biology, University of Texas MD Anderson Cancer CenterHoustonUnited States
| | - Raghu Kalluri
- Department of Cancer Biology, University of Texas MD Anderson Cancer CenterHoustonUnited States
- Department of Bioengineering, Rice UniversityHoustonUnited States
- Department of Molecular and Cellular Biology, Baylor College of MedicineHoustonUnited States
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Li B, Kugeratski FG, Kalluri R. A novel machine learning algorithm selects proteome signature to specifically identify cancer exosomes. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.07.18.549557. [PMID: 37503071 PMCID: PMC10370082 DOI: 10.1101/2023.07.18.549557] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/29/2023]
Abstract
Non-invasive early cancer diagnosis remains challenging due to the low sensitivity and specificity of current diagnostic approaches. Exosomes are membrane-bound nanovesicles secreted by all cells that contain DNA, RNA, and proteins that are representative of the parent cells. This property, along with the abundance of exosomes in biological fluids makes them compelling candidates as biomarkers. However, a rapid and flexible exosome-based diagnostic method to distinguish human cancers across cancer types in diverse biological fluids is yet to be defined. Here, we describe a novel machine learning-based computational method to distinguish cancers using a panel of proteins associated with exosomes. Employing datasets of exosome proteins from human cell lines, tissue, plasma, serum and urine samples from a variety of cancers, we identify Clathrin Heavy Chain (CLTC), Ezrin, (EZR), Talin-1 (TLN1), Adenylyl cyclase-associated protein 1 (CAP1) and Moesin (MSN) as highly abundant universal biomarkers for exosomes and define three panels of pan-cancer exosome proteins that distinguish cancer exosomes from other exosomes and aid in classifying cancer subtypes employing random forest models. All the models using proteins from plasma, serum, or urine-derived exosomes yield AUROC scores higher than 0.91 and demonstrate superior performance compared to Support Vector Machine, K Nearest Neighbor Classifier and Gaussian Naive Bayes. This study provides a reliable protein biomarker signature associated with cancer exosomes with scalable machine learning capability for a sensitive and specific non-invasive method of cancer diagnosis.
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YANG HONG, LI WAN, REN LIWEN, YANG YIHUI, ZHANG YIZHI, GE BINBIN, LI SHA, ZHENG XIANGJIN, LIU JINYI, ZHANG SEN, DU GUANHUA, TANG BO, WANG HONGQUAN, WANG JINHUA. Progress on diagnostic and prognostic markers of pancreatic cancer. Oncol Res 2023; 31:83-99. [PMID: 37304241 PMCID: PMC10208033 DOI: 10.32604/or.2023.028905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 02/15/2023] [Indexed: 06/13/2023] Open
Abstract
Pancreatic cancer is a malignant disease characterized by low survival and high recurrence rate, whose patients are mostly at the stage of locally advanced or metastatic disease when first diagnosed. Early diagnosis is particularly important because prognostic/predictive markers help guide optimal individualized treatment regimens. So far, CA19-9 is the only biomarker for pancreatic cancer approved by the FDA, but its effectiveness is limited by low sensitivity and specificity. With recent advances in genomics, proteomics, metabolomics, and other analytical and sequencing technologies, the rapid acquisition and screening of biomarkers is now possible. Liquid biopsy also occupies a significant place due to its unique advantages. In this review, we systematically describe and evaluate the available biomarkers that have the greatest potential as vital tools in diagnosing and treating pancreatic cancer.
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Affiliation(s)
- HONG YANG
- The State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing, 100050, China
- Key Laboratory of Drug Target Research and Drug Screen, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China
| | - WAN LI
- The State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing, 100050, China
- Key Laboratory of Drug Target Research and Drug Screen, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China
| | - LIWEN REN
- The State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing, 100050, China
- Key Laboratory of Drug Target Research and Drug Screen, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China
| | - YIHUI YANG
- The State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing, 100050, China
- Key Laboratory of Drug Target Research and Drug Screen, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China
| | - YIZHI ZHANG
- The State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing, 100050, China
- Key Laboratory of Drug Target Research and Drug Screen, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China
| | - BINBIN GE
- The State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing, 100050, China
- Key Laboratory of Drug Target Research and Drug Screen, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China
| | - SHA LI
- The State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing, 100050, China
- Key Laboratory of Drug Target Research and Drug Screen, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China
| | - XIANGJIN ZHENG
- The State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing, 100050, China
- Key Laboratory of Drug Target Research and Drug Screen, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China
| | - JINYI LIU
- The State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing, 100050, China
- Key Laboratory of Drug Target Research and Drug Screen, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China
| | - SEN ZHANG
- The State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing, 100050, China
- Key Laboratory of Drug Target Research and Drug Screen, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China
| | - GUANHUA DU
- The State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing, 100050, China
- Key Laboratory of Drug Target Research and Drug Screen, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China
| | - BO TANG
- Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China
| | - HONGQUAN WANG
- Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China
| | - JINHUA WANG
- The State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing, 100050, China
- Key Laboratory of Drug Target Research and Drug Screen, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China
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Liver Tumor Markers, HALP Score, and NLR: Simple, Cost-Effective, Easily Accessible Indexes for Predicting Prognosis in ICC Patients after Surgery. J Pers Med 2022; 12:jpm12122041. [PMID: 36556261 PMCID: PMC9784982 DOI: 10.3390/jpm12122041] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Revised: 12/01/2022] [Accepted: 12/08/2022] [Indexed: 12/14/2022] Open
Abstract
INTRODUCTION To investigate the prognostic significance of liver tumor markers, the hemoglobin, albumin, lymphocyte, and platelet (HALP) score; neutrophil-to-lymphocyte ratio (NLR); and platelet-to-lymphocyte ratio (PLR), for predicting the specific site of recurrence or metastasis after surgery in patients with intrahepatic cholangiocarcinoma (ICC). METHODS In total, 162 patients with pathologically proven ICC who underwent curative surgery at Sun Yat-sen University Cancer Center between April 2016 and April 2020 were analyzed. Clinicopathological characteristics were collected retrospectively. The Kaplan-Meier method was used to analyze the overall survival (OS) and recurrence-free survival (RFS). Significant clinical factors were examined by univariate analysis and multivariate analysis and analyzed by receiver operating characteristic (ROC) curve analysis. RESULTS The cutoff values for the HALP score, NLR, and PLR were determined to be 43.63, 3.73, and 76.51, respectively, using the surv_cutpoint function of survminer using RFS as the target variable. In multivariate analysis, vascular invasion, pathology nerve tract invasion, and carbohydrate antigen 19-9 (CA19-9) levels were independent prognostic factors of OS, whereas the tumor number, pathology microvascular invasion, pathology differentiation, CA19-9 levels, and NLR were independent prognostic factors of RFS. For the whole recurrence analysis, the carcinoembryonic antigen (CEA) index exhibited the largest ROC curve area of all (AUC = 0.590), and the alpha-fetoprotein (AFP) index exhibited the smallest ROC curve area (AUC = 0.530). The HALP score exhibited the largest ROC curve area of all in predicting intrahepatic recurrence (AUC = 0.588), the NLR showed the best predictive value in predicting lymph node metastasis (AUC = 0.703), and the AUC of the CA19-9 index was the largest of all variables in predicting distant metastasis (AUC = 0.619). CONCLUSIONS Our study showed that CA19-9, CEA, HALP score, and NLR are easily accessible, reliable, cost-effective indexes for predicting the specific site of recurrence or metastasis after surgery in ICC patients. Patients with high HALP scores and NLR have a higher risk of intrahepatic and lymph node metastasis recurrence.
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Wei A, Zhao H, Cong X, Wang L, Chen Y, Gou J, Hu Z, Hu X, Tian Y, Li K, Deng Y, Zuo H, Fu MR. Oral mycobiota and pancreatic ductal adenocarcinoma. BMC Cancer 2022; 22:1251. [PMID: 36460974 PMCID: PMC9716801 DOI: 10.1186/s12885-022-10329-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Accepted: 11/17/2022] [Indexed: 12/05/2022] Open
Abstract
Early detection of pancreatic ductal adenocarcinoma (PDAC) is essential for survival. Preliminary research demonstrated significant associations between structural alternation of mycobiota and PDAC. In this study, we investigated the associations between oral mycobiota and PDAC. We further explored mycobiota biomarkers for PDAC detection. We enrolled 34 PDAC patients and 35 matched healthy controls from West China hospital in Southwest China. Demographic data, clinical information, and salivary samples were collected. Mycobiota characteristics were defined using Internal Transcribed Spacer (ITS) ribosomal RNA sequencing. We found that the PDAC patients had significant increase in fungal abundance (P < 0.001) and significant decrease in fungal diversity (P < 0.001) in comparison to the healthy controls. A higher abundance of Basidiomycota and Unclassifed_p_Ascomycota was associated with an increased risk of PDAC. With each increase of abundance of g__unclassified_k__Fungi and g__unclassified_p__Ascomycota in PDAC patients, the risk of pancreatic cancer increased by 1.359 odds and 1.260 odds, respectively. Aspergillus (AUC = 0.983, 95% CI 0.951-1.000) and Cladosporium (AUC = 0.969, 95% CI 0.921-1.000) achieved high classification powers to distinguish PDAC patients from the healthy controls. The rapid, inexpensive tests of ITS1 sequencing of mycobiota and PCR detection of potential fungal biomarkers make it promising for the clinical practice to use oral microbes for PDAC early detection and prevention. Results of our study provide evidence that salivary mycobiota may provide insights into cancer risk, prevention, and detection.
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Affiliation(s)
- Ailin Wei
- Guang’an People’s Hospital, Sichuan Province, Guang’an, 638001 China
| | - Huiling Zhao
- grid.13291.380000 0001 0807 1581West China School of Nursing/Department of Otolaryngology-Head and Neck Surgery, West China Hospital, Sichuan University, Sichuan Province, Chengdu, 610041 China
| | - Xue Cong
- grid.13291.380000 0001 0807 1581West China School of Public Health/West China Fourth Hospital, Sichuan University, No. 16, Section 3, Renmin South Road, Wuhou District, Chengdu, 610041 Sichuan China
| | - Linyao Wang
- grid.13291.380000 0001 0807 1581West China School of Public Health/West China Fourth Hospital, Sichuan University, No. 16, Section 3, Renmin South Road, Wuhou District, Chengdu, 610041 Sichuan China
| | - Yiyang Chen
- grid.13291.380000 0001 0807 1581West China School of Public Health/West China Fourth Hospital, Sichuan University, No. 16, Section 3, Renmin South Road, Wuhou District, Chengdu, 610041 Sichuan China
| | - Juxiang Gou
- grid.13291.380000 0001 0807 1581West China School of Nursing/West China Hospital, Sichuan University, Sichuan Province, Chengdu, 610041 China
| | - Ziyi Hu
- grid.13291.380000 0001 0807 1581West China School of Nursing/West China Hospital, Sichuan University, Sichuan Province, Chengdu, 610041 China
| | - Xiuying Hu
- grid.13291.380000 0001 0807 1581West China School of Nursing/West China Hospital, Sichuan University, Sichuan Province, Chengdu, 610041 China
| | - Yali Tian
- grid.13291.380000 0001 0807 1581West China School of Nursing/West China Hospital, Sichuan University, Sichuan Province, Chengdu, 610041 China
| | - Ka Li
- grid.13291.380000 0001 0807 1581West China School of Nursing/West China Hospital, Sichuan University, Sichuan Province, Chengdu, 610041 China
| | - Yufeng Deng
- grid.13291.380000 0001 0807 1581West China School of Public Health/West China Fourth Hospital, Sichuan University, No. 16, Section 3, Renmin South Road, Wuhou District, Chengdu, 610041 Sichuan China
| | - Haojiang Zuo
- grid.13291.380000 0001 0807 1581West China School of Public Health/West China Fourth Hospital, Sichuan University, No. 16, Section 3, Renmin South Road, Wuhou District, Chengdu, 610041 Sichuan China ,grid.13291.380000 0001 0807 1581West China School of Nursing/West China Hospital, Sichuan University, Sichuan Province, Chengdu, 610041 China
| | - Mei Rosemary Fu
- grid.430387.b0000 0004 1936 8796Rutgers University, School of Nursing–Camden, 530 Federal Street, Camden, NJ 08102 USA
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Seyed Salehi A, Parsa-Nikoo N, Roshan-Farzad F, Shams R, Fathi M, Asaszadeh Aghdaei H, Behmanesh A. MicroRNA-125a-3p, -4530, and -92a as a Potential Circulating MicroRNA Panel for Noninvasive Pancreatic Cancer Diagnosis. DISEASE MARKERS 2022; 2022:8040419. [PMID: 36254252 PMCID: PMC9569215 DOI: 10.1155/2022/8040419] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Revised: 08/18/2022] [Accepted: 09/21/2022] [Indexed: 12/24/2022]
Abstract
MicroRNA (miRNA) expression dysregulations in pancreatic ductal adenocarcinoma (PDAC) have been studied widely for their diagnostic and prognostic utility. By the use of bioinformatics-based methods, in our previous study, we identified some potential miRNA panels for diagnosis of pancreatic cancer patients from noncancerous controls (the screening stage). In this report, we used 142 plasma samples from people with and without pancreatic cancer (PC) to conduct RT-qPCR differential expression analysis to assess the strength of the first previously proposed diagnostic panel (consisting of miR-125a-3p, miR-4530, and miR-92a-2-5p). As the result, we identified significant upregulation for all the three considered miRNAs in the serum of PC patients. After that, a three-miRNA panel in serum was developed. The area under the receiver operating characteristic curves (AUC) for the panel were 0.850, 0.910, and 0.86, respectively, indicating that it had a higher diagnostic value than individual miRNAs. Therefore, we detected a promising three-miRNA panel in the plasma for noninvasive PC diagnosis (miR-125a-3p, miR-4530, and miR-92a-2-5p).
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Affiliation(s)
- Ali Seyed Salehi
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Department of Biology, Faculty of Biological Science, Islamic Azad University, North Tehran Branch, Tehran, Iran
| | - Negar Parsa-Nikoo
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Department of Biology, Faculty of Biological Science, Islamic Azad University, North Tehran Branch, Tehran, Iran
| | - Farnaz Roshan-Farzad
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Department of Biology, Faculty of Biological Science, Islamic Azad University, North Tehran Branch, Tehran, Iran
| | - Roshanak Shams
- Bone and Joint Reconstruction Research Center, Department of Orthopedics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mohadeseh Fathi
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamid Asaszadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Behmanesh
- Bone and Joint Reconstruction Research Center, Department of Orthopedics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
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10
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Gan L, Ren S, Lang M, Li G, Fang F, Chen L, Liu Y, Han R, Zhu K, Song T. Predictive Value of Preoperative Serum AFP, CEA, and CA19-9 Levels in Patients with Single Small Hepatocellular Carcinoma: Retrospective Study. J Hepatocell Carcinoma 2022; 9:799-810. [PMID: 35990213 PMCID: PMC9384872 DOI: 10.2147/jhc.s376607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Accepted: 08/04/2022] [Indexed: 11/23/2022] Open
Abstract
Purpose This study aimed to explore the relationship between the tumor marker score (TMS) and the postoperative recurrence of single small hepatocellular carcinoma (HCC). Patients and Methods A total of 409 patients with one resectable HCC with a diameter of 3 cm or less who visited Tianjin Medical University Cancer Institute & Hospital from January 2010 to December 2014 were included in this study. Their alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) levels were classified into low and high groups using X-tile software. Each patients' TMS was calculated as the sum of each tumor marker (low = 0; high = 1). Results A total of 142 patients were classified as TMS0, 171 as TMS1, and 96 as TMS2. Kaplan–Meier analysis illustrated that TMS could divide the patients into groups with remarkably different prognoses, and the patients with high TMS had worse recurrence-free survival (RFS) than those with low TMS. Multivariate analysis showed that TMS, age, and HBeAg positive were the independent predictors of RFS rate. Subgroup analysis revealed that high TMS was a stable risk factor relative to TMS0. Receiver operating curves showed that the 1-, 3-, and 5-year area under curve (AUC) values of TMS were 0.698, 0.662, and 0.673, respectively. The AUC of TMS was higher than that of other common prognostic models in time-dependent receiver operating curve. Conclusion TMS was an independent prognostic factor for the postoperative recurrence of a single small HCC and can provide a well-discriminated risk stratification, thus contributing to prognostic prediction and adjuvant therapeutic development.
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Affiliation(s)
- Leijuan Gan
- Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China
| | - Shaohua Ren
- Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China
| | - Mengran Lang
- Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China
| | - Guangtao Li
- Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China
| | - Feng Fang
- Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China
| | - Lu Chen
- Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China
| | - Yayue Liu
- Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China
| | - Ruyu Han
- Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China
| | - Kangwei Zhu
- Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China
| | - Tianqiang Song
- Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China
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11
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Toyoda J, Sahara K, Maithel SK, Abbott DE, Poultsides GA, Wolfgang C, Fields RC, He J, Scoggins C, Idrees K, Shen P, Endo I, Pawlik TM. Prognostic Utility of Systemic Immune-Inflammation Index After Resection of Extrahepatic Cholangiocarcinoma: Results from the U.S. Extrahepatic Biliary Malignancy Consortium. Ann Surg Oncol 2022; 29:7605-7614. [PMID: 35768667 DOI: 10.1245/s10434-022-12058-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 06/05/2022] [Indexed: 12/18/2022]
Abstract
BACKGROUND We sought to define the association of the systemic immune inflammation index (SII) with prognosis and adjuvant therapy benefit among patients undergoing resection of extrahepatic cholangiocarcinoma (eCCA). METHODS The impact of SII on overall (OS) and recurrence-free survival (RFS) following resection of eCCA was assessed and compared with other inflammatory markers and traditional prognostic factors. Propensity score matching (PSM) was used to determine the impact of adjuvant therapy (AT) on OS and RFS relative to low versus high SII. RESULTS Patients with high versus low SII had worse 5-year OS (15.9% vs. 27.9%) and RFS (12.4% vs. 20.9%) (both p < 0.01). On multivariate analysis, high SII remained associated with worse OS (HR = 1.50, 95% CI 1.20-1.87) and RFS (HR = 1.46, 95% CI 1.18-1.81). Patients with T1/2 disease and a high-SII had worse 5-year OS versus individuals with T3/4 disease and low-SII (5-year OS: T1/2 & low-SII 35.6%, T1/2 & high-SII 16.4%, T3/4 & low-SII 22.1%, T3/4 & high-SII 15.6%, p < 0.01). Similarly, 5-year OS was comparable among individuals with N0 and high-SII versus N1 and low-SII (5-year OS: N0 & high-SII 23.2%, N1 and low-SII 19.8%, p = 0.95). On PSM, AT improved OS and RFS among patients with high SII (5-year OS: 22.5% vs. 12.3%, p < 0.01, 5-year RFS: 19.0% vs. 12.5%; p = 0.01) but not individuals with low SII (5-year OS: 22.9% vs. 26.9%; p = 0.98, 5-year RFS: 18.5% vs. 19.9%; p = 0.94). CONCLUSIONS SII was independently associated with postoperative OS and RFS following curative-intent resection of eCCA. High SII up-staged patients relative T- and N-categories and identified patients with high SII as the most likely to benefit from AT.
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Affiliation(s)
- Junya Toyoda
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Kota Sahara
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan.,Department of Surgery, The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH, USA
| | - Shishir K Maithel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Daniel E Abbott
- Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA
| | - George A Poultsides
- Department of Surgery, Stanford University Medical Center, Stanford, CA, USA
| | | | - Ryan C Fields
- Department of Surgery, Washington University School of Medicine, St Louis, MO, USA
| | - Jin He
- Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Charles Scoggins
- Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, KY, USA
| | - Kamran Idrees
- Division of Surgical Oncology, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Perry Shen
- Department of Surgery, Wake Forest University, Winston-Salem, NC, USA
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH, USA.
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12
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Zhao C, Zhang X, Chen G, Shang L. Developing sensor materials for screening intestinal diseases. MATERIALS FUTURES 2022; 1:022401. [DOI: 10.1088/2752-5724/ac48a3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Abstract
Intestinal diseases that have high mortality and morbidity rates and bring huge encumbrance to the public medical system and economy worldwide, have always been the focus of clinicians and scientific researchers. Early diagnosis and intervention are valuable in the progression of many intestinal diseases. Fortunately, the emergence of sensor materials can effectively assist clinical early diagnosis and health monitoring. By accurately locating the lesion and sensitively analyzing the level of disease markers, these sensor materials can help to precisely diagnose the stage and state of lesions, thereby avoiding delayed treatment. In this review, we provide comprehensive and in-depth knowledge of diagnosing and monitoring intestinal diseases with the assistance of sensor materials, particularly emphasizing their design and application in bioimaging and biodetection. This review is dedicated to conveying practical applications of sensor materials in the intestine, critical analysis of their mechanisms and applications and discussion of their future roles in medicine. We believe that this review will promote multidisciplinary communication between material science, medicine and relevant engineering fields, thus improving the clinical translation of sensor materials.
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13
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Xu Y, Xiong Q, Yang Y, Weng N, Li J, Liu J, Yang X, Zeng Z, Zhang Z, Zhu Q. Serum Nardilysin as a Prognostic Biomarker in Pancreatic Ductal Adenocarcinoma. J Clin Med 2022; 11:jcm11113101. [PMID: 35683488 PMCID: PMC9181681 DOI: 10.3390/jcm11113101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 05/20/2022] [Accepted: 05/25/2022] [Indexed: 11/29/2022] Open
Abstract
Background: Nardilysin, (N-arginine dibasic convertase, NRDC) has been reported to play an important role in cancer progression, and is associated with tumor proliferation signals and inflammatory signals, such as tumor necrosis factor-a (TNF-a) and heparin-binding epidermal growth factor-like growth factor (HB-EGF), through the activation of disintegrin and metalloproteinase (ADAM) proteases. NRDC has recently been revealed to be involved in the tumorigenesis of various types of cancer, including intrahepatic cholangiocarcinoma, malignant cerebral infarction, esophageal squamous cell carcinoma, and gastric cancer. However, the expression profiles and biological relevance of NRDC in pancreatic ductal adenocarcinoma have rarely been reported. Methods: We analyzed the NRDC expression profile in pancreatic ductal adenocarcinoma by enzyme-linked immunosorbent assay (ELISA) and identified NRDC as a circulating biomarker in the serum of 112 pancreatic ductal adenocarcinoma patients. The diagnostic value of NRDC was analyzed by the area under the curve (AUC) and the receiver operating characteristic (ROC) test. Results: Our results demonstrated that the clinical prognosis significance of NRDC with the clinical characteristics in pancreatic ductal adenocarcinoma (PDAC). NRDC was notably decreased in PDAC patient serum compared with the control group (p < 0.001). Furthermore, the present study found that the NRDC expression level was correlated with T grade (p < 0.001), metastasis(p < 0.001), differentiation(p < 0.001), and TNM stage (p = 0.011). Further bioinformatics analysis revealed that NRDC correlated with proliferation and migration pathways; in particular, it mediated cell-matrix adhesion-dependent activation in pancreatic ductal adenocarcinoma. Conclusions: Serum NRDC may play a useful diagnostic biomarker to evaluate the aggressive clinical features in PAAD patients.
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14
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Zhang W, Wang Y, Dong X, Yang B, Zhou H, Chen L, Zhang Z, Zhang Q, Cao G, Han Z, Li H, Cui Y, Wu Q, Zhang T, Song T, Li Q. Elevated serum CA19-9 indicates severe liver inflammation and worse survival after curative resection in hepatitis B-related hepatocellular carcinoma. Biosci Trends 2021; 15:397-405. [PMID: 34880159 DOI: 10.5582/bst.2021.01517] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
We explored the prognostic value of preoperative CA19-9 in α-fetoprotein (AFP)-positive and -negative HCC with hepatitis B virus (HBV) background (HBV-HCC), and explored the underlying mechanism. Recurrence-free survival (RFS) and overall survival (OS) were assessed in HBV-HCC patients who underwent curative resection (Cohort 1). Immunohistochemical staining of CA19-9 in HCC and liver parenchyma were quantified in another cohort of 216 patients with resected HCC (Cohort 2). Immunohistochemical staining of CA19-9 and serum CA19-9 level was also compared between patients with HCC and intrahepatic cholangiocarcinoma (ICC) (Cohort 3). In Cohort 1, CA19-9 ≥ 39 U/mL was an independent risk factor for RFS (HR = 1.507, 95% CI = 1.087-2.091, p = 0.014) and OS (HR = 1.646, 95% CI = 1.146-2.366, p = 0.007). CA19-9 ≥ 39 U/mL was also associated with significantly higher incidence of macrovascular invasion (MaVI) compared with CA19-9 < 39 U/mL (23.0% vs. 7.2%, p = 0.002), and elevated aminotransferase and aspartate aminotransferase to platelet ratio index (APRI), and lower albumin. Immunohistochemical staining of CA19-9 revealed that CA19-9 expression was found exclusively in the background liver but not in HCC tumor cells. In contrast, tumor tissue was the main source of CA19-9 in ICC patients. CA19-9 ≥ 39 U/mL was associated with worse OS and RFS in both AFP-positive and negative HCC patients. CA19-9 indicated more severe inflammation and cirrhosis in the liver of HCC patients.
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Affiliation(s)
- Wei Zhang
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital; Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Yingying Wang
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital; Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Xiang Dong
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital; Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, China.,Department of Department of General Surgery, Hebei Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Cangzhou City, Hebei Province, China
| | - Bo Yang
- Department of Pathology, Tianjin Medical University Cancer Institute and Hospital; Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Hongyuan Zhou
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital; Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Lu Chen
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital; Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Zewu Zhang
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital; Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Qin Zhang
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital; Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Guangtai Cao
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital; Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Zhiqiang Han
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital; Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Huikai Li
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital; Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Yunlong Cui
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital; Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Qiang Wu
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital; Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Ti Zhang
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital; Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Tianqiang Song
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital; Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Qiang Li
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital; Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, China
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15
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Kang JS, Hong SY, Han Y, Sohn HJ, Lee M, Kang YH, Kim HS, Kim H, Kwon W, Jang JY. Limits of serum carcinoembryonic antigen and carbohydrate antigen 19-9 as the diagnosis of gallbladder cancer. Ann Surg Treat Res 2021; 101:266-273. [PMID: 34796142 PMCID: PMC8564080 DOI: 10.4174/astr.2021.101.5.266] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 07/01/2021] [Accepted: 09/24/2021] [Indexed: 12/29/2022] Open
Abstract
Purpose Although serum CEA and CA 19-9 have been widely utilized for the diagnosis of gallbladder cancer (GBC), few studies have examined the diagnostic performance of them. This study aimed to investigate the diagnostic performance of these 2 biomarkers and demonstrate their clinical usefulness in diagnosing GBC. Methods Between January 2000 and March 2020, a total of 751 GBC patients and 2,310 normal controls were included. Serum CEA and CA 19-9 were measured preoperatively. Receiver operating characteristic curves were obtained, and the sensitivity and specificity of each biomarker were evaluated. Results In terms of differentiating GBC from the control, the sensitivity and specificity of serum CEA at 5 ng/mL was 12.1% and 99.1%, respectively, and those of serum CA 19-9 at 37 IU/mL were 28.7% and 94.5%, respectively. The optimal cutoff values of CEA and CA 19-9 were set to 2.1 ng/mL and 26 IU/mL in the receiver operating characteristic curves, respectively. The sensitivities of CEA and CA 19-9 at new cutoff values slightly increased but remained low (CEA, 42.9%; CA 19-9, 38.2%). When differentiating early-stage GBC from advanced tumor, the sensitivity and specificity, were 14.2% and 96.1% for CEA (cutoff value, 5 ng/mL) and 33.6% and 90.1% for CA 19-9 (cutoff value, 37 IU/mL), respectively. Conclusion Serum CEA and CA 19-9 levels are not suitable for screening GBC patients from controls. New promising biomarkers with higher sensitivity should be explored.
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Affiliation(s)
- Jae Seung Kang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Su Young Hong
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Youngmin Han
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hee Ju Sohn
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Mirang Lee
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Yoon Hyung Kang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hyeong Seok Kim
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hongbeom Kim
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Wooil Kwon
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jin-Young Jang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
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16
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Kim HS, Han Y, Kang JS, Kang YH, Lee M, Sohn HJ, Kim H, Kwon W, Jang JY. Serum carcinoembryonic antigen and carbohydrate antigen 19-9 as preoperative diagnostic biomarkers of extrahepatic bile duct cancer. BJS Open 2021; 5:zrab127. [PMID: 34935900 PMCID: PMC8693162 DOI: 10.1093/bjsopen/zrab127] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Accepted: 11/07/2021] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND Serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 have been proposed as useful preoperative biomarkers of extrahepatic bile duct cancer (EBDC). This study investigated the accuracy of CEA and CA19-9 for preoperative diagnosis of EBDC. METHODS Patients who underwent surgery for EBDC at a tertiary centre between 1995 and 2018 were studied, and those with concurrent hepatobiliary diseases (including gallbladder cancer, intraductal papillary mucinous neoplasms of pancreas), which could affect CEA or CA19-9 levels, were excluded. The control group included patients who underwent cholecystectomy for benign gallbladder diseases during the same period. Diagnostic accuracy was determined using sensitivity, specificity and area under the receiver operating characteristic curve (AUC). RESULTS After excluding 23 patients, 687 patients (488 men and 199 women, mean age 65.8 years) were compared with the control group of 2310 patients. Median CEA and CA19-9 levels were 1.8 μg/l and 47.0 kU/l in patients with EBDC. CEA (cut-off 5.0 μg/l) showed AUC of 0.541, sensitivity 9.0 per cent and specificity 99.2 per cent, whereas CA19-9 (cut-off 37.0 kU/l) showed AUC of 0.753, sensitivity 56.2 per cent and specificity 94.5 per cent. Sensitivity of CA19-9 was lower in early (T stages 0-II) than advanced (T stages III and IV) cancer (47.0 versus 64.9 per cent), and also lower in N0 stage cancer than lymph node metastasis (50.1 versus 68.8 per cent). CONCLUSION Serum CEA and CA19-9 showed low sensitivity limiting their usefulness as diagnostic biomarkers of EBDC.
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Affiliation(s)
- Hyeong Seok Kim
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Youngmin Han
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Jae Seung Kang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Yoon Hyung Kang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Mirang Lee
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Hee Ju Sohn
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Hongbeom Kim
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Wooil Kwon
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Jin-Young Jang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
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17
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Jun E, Koo B, Kim EJ, Hwang DW, Lee JH, Song KB, Lee W, Park Y, Hong S, Shin Y, Kim SC. Analysis of KRAS Mutation Subtype in Tissue DNA and Cell-Free DNA Using Droplet Digital PCR and the Function of Cell-Free DNA as a Recurrence Predictive Marker in Pancreatic Cancer. Biomedicines 2021; 9:1599. [PMID: 34829828 PMCID: PMC8615414 DOI: 10.3390/biomedicines9111599] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 10/26/2021] [Accepted: 10/30/2021] [Indexed: 11/17/2022] Open
Abstract
KRAS mutation is a major regulator in the tumor progression of pancreatic cancer. Here, we compared the frequency and mutation burden of KRAS mutation subtypes with paired tumor tissue and blood in patients and examined their clinical significance. DNA from tumor tissues and cell-free DNA (cfDNA) from preoperative blood were obtained from 70 patients with pancreatic cancer. Subtypes and mutation burdens of KRAS G12D and G12V mutations were evaluated using droplet digital PCR. Comparing the presence of mutations in tissue, accumulative and simultaneous mutations of G12D or G12V were identified of 67 (95.7%), and 48 patients (68.6%). Conversely, in blood, they were only identified in 18 (25.7%) and four (5.7%) patients; respectively. Next, comparing the mutation burden in tissue, the mutation burden varied from less than 0.1 to more than five, whereas that of cfDNA in blood was mostly between one and five, as cases with a mutation burden lower than 0.1 and higher than five were rare. Finally, the presence of the G12V mutation alone in cfDNA and the combination of the G12V mutation with elevated CA 19-9 levels were associated with poor recurrence-free survival. These fundamental data on the KRAS mutation subtypes and their clinical significance could support their potential as predictive markers for postoperative recurrence.
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Affiliation(s)
- Eunsung Jun
- Department of Convergence Medicine, Asan Institute for Life Sciences, University of Ulsan College of Medicine and Asan Medical Center, Seoul 05505, Korea;
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, AMIST, University of Ulsan College of Medicine, Seoul 05505, Korea; (D.W.H.); (J.H.L.); (K.B.S.); (W.L.); (Y.P.); (S.H.)
| | - Bonhan Koo
- Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea;
| | - Eo Jin Kim
- Department of Convergence Medicine, Asan Institute for Life Sciences, University of Ulsan College of Medicine and Asan Medical Center, Seoul 05505, Korea;
| | - Dae Wook Hwang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, AMIST, University of Ulsan College of Medicine, Seoul 05505, Korea; (D.W.H.); (J.H.L.); (K.B.S.); (W.L.); (Y.P.); (S.H.)
| | - Jae Hoon Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, AMIST, University of Ulsan College of Medicine, Seoul 05505, Korea; (D.W.H.); (J.H.L.); (K.B.S.); (W.L.); (Y.P.); (S.H.)
| | - Ki Byung Song
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, AMIST, University of Ulsan College of Medicine, Seoul 05505, Korea; (D.W.H.); (J.H.L.); (K.B.S.); (W.L.); (Y.P.); (S.H.)
| | - Woohyung Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, AMIST, University of Ulsan College of Medicine, Seoul 05505, Korea; (D.W.H.); (J.H.L.); (K.B.S.); (W.L.); (Y.P.); (S.H.)
| | - Yejong Park
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, AMIST, University of Ulsan College of Medicine, Seoul 05505, Korea; (D.W.H.); (J.H.L.); (K.B.S.); (W.L.); (Y.P.); (S.H.)
| | - Sarang Hong
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, AMIST, University of Ulsan College of Medicine, Seoul 05505, Korea; (D.W.H.); (J.H.L.); (K.B.S.); (W.L.); (Y.P.); (S.H.)
| | - Yong Shin
- Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea;
| | - Song Cheol Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, AMIST, University of Ulsan College of Medicine, Seoul 05505, Korea; (D.W.H.); (J.H.L.); (K.B.S.); (W.L.); (Y.P.); (S.H.)
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Perales S, Torres C, Jimenez-Luna C, Prados J, Martinez-Galan J, Sanchez-Manas JM, Caba O. Liquid biopsy approach to pancreatic cancer. World J Gastrointest Oncol 2021; 13:1263-1287. [PMID: 34721766 PMCID: PMC8529923 DOI: 10.4251/wjgo.v13.i10.1263] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Revised: 05/18/2021] [Accepted: 08/27/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cancer (PC) continues to pose a major clinical challenge. There has been little improvement in patient survival over the past few decades, and it is projected to become the second leading cause of cancer mortality by 2030. The dismal 5-year survival rate of less than 10% after the diagnosis is attributable to the lack of early symptoms, the absence of specific biomarkers for an early diagnosis, and the inadequacy of available chemotherapies. Most patients are diagnosed when the disease has already metastasized and cannot be treated. Cancer interception is vital, actively intervening in the malignization process before the development of a full-blown advanced tumor. An early diagnosis of PC has a dramatic impact on the survival of patients, and improved techniques are urgently needed to detect and evaluate this disease at an early stage. It is difficult to obtain tissue biopsies from the pancreas due to its anatomical position; however, liquid biopsies are readily available and can provide useful information for the diagnosis, prognosis, stratification, and follow-up of patients with PC and for the design of individually tailored treatments. The aim of this review was to provide an update of the latest advances in knowledge on the application of carbohydrates, proteins, cell-free nucleic acids, circulating tumor cells, metabolome compounds, exosomes, and platelets in blood as potential biomarkers for PC, focusing on their clinical relevance and potential for improving patient outcomes.
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Affiliation(s)
- Sonia Perales
- Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Granada 18071, Spain
| | - Carolina Torres
- Department of Biochemistry and Molecular Biology III and Immunology, Faculty of Sciences, University of Granada, Granada 18071, Spain
| | - Cristina Jimenez-Luna
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada 18100, Spain
| | - Jose Prados
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada 18100, Spain
| | - Joaquina Martinez-Galan
- Department of Medical Oncology, Hospital Universitario Virgen de las Nieves, Granada 18011, Spain
| | | | - Octavio Caba
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada 18100, Spain
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Wang S, You L, Dai M, Zhao Y. Quantitative assessment of the diagnostic role of mucin family members in pancreatic cancer: a meta-analysis. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:192. [PMID: 33708819 PMCID: PMC7940915 DOI: 10.21037/atm-20-5606] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Background The use of mucins (MUC) as specific biomarkers for various malignancies has recently emerged. MUC1, MUC4, MUC5AC, and MUC16 can be detected at different stages of pancreatic cancer (PC), and can be valuable for indicating the initiation and progression of this disease. However, the diagnostic significance of the mucin family in patients with PC remains disputed. Herein, we assessed the diagnostic accuracy of mucins in PC using a meta-analysis. Methods We searched the PubMed, Cochrane Library, Institute for Scientific Information (ISI) Web of Science, Embase, and Chinese databases from their date of inception to June 1, 2020 to identify studies assessing the diagnostic performance of mucins in PC. The estimations of diagnostic indicators in selected studies were extracted for further analysis by Meta-DiSc software. Publication bias was assessed using Deeks’ funnel plot asymmetry test. Results Our meta-analysis included 34 studies. The pooled accuracy indicators of MUC1 in PC including the sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) (with 95% confidence intervals) were 0.84 (0.82–0.86), 0.60 (0.56–0.64), 18.37 (9.18–36.78), 2.62 (1.79–3.86), and 0.22 (0.15–0.33), respectively. The area under the summary receiver operating characteristic (SROC) curve was 0.8875 and the Q index was 0.8181. Quantitative random-effects meta-analysis of MUC4 in PC using the summary (ROC) curve model revealed a pooled sensitivity of 0.86 (95% confidence interval, 0.82–0.89) and specificity of 0.88 (95% confidence interval, 0.85–0.91). In addition, the meta-analysis of MUC5AC in PC diagnosis also showed a high sensitivity and specificity of 0.71 (95% confidence interval, 0.65–0.76) and 0.60 (95% confidence interval, 0.53–0.66), respectively. Regarding MUC16, the area under the summary ROC curve and Q index were 0.9185 and 0.8516, respectively. Conclusions In summary, our results suggested a good diagnostic accuracy of several crucial mucins in PC. Mucins may serve as optional indicators in PC examination, and further research is warranted to investigate the role of mucins as potential clinical biomarkers.
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Affiliation(s)
- Shunda Wang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lei You
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Menghua Dai
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yupei Zhao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Ren AH, Prassas I, Soosaipillai A, Jarvi S, Gallinger S, Kulasingam V, Diamandis EP. Investigating a novel multiplex proteomics technology for detection of changes in serum protein concentrations that may correlate to tumor burden. F1000Res 2020; 9:732. [PMID: 33274048 PMCID: PMC7682495 DOI: 10.12688/f1000research.24654.2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/04/2020] [Indexed: 12/30/2022] Open
Abstract
Background: To account for cancer heterogeneity, we previously introduced the concept of "personalized" tumor markers, which are biomarkers that are informative in subsets of patients or even a single patient. Recent developments in various multiplex protein technologies create excitement for the discovery of markers of tumor burden in individual patients, but the reliability of the technologies remains to be tested for this purpose. Here, we sought to explore the potential of a novel proteomics platform, which utilizes a multiplexed antibody microarray, to detect changes in serum protein concentration that may correlate to tumor burden in pancreatic cancer. Methods: We applied the Quantibody® Human Kiloplex Array to simultaneously measure 1,000 proteins in sera obtained pre- and post-surgically from five pancreatic cancer patients. We expected that proteins which decreased post-surgery may correlate to tumor burden. Sera from two healthy individuals, split into two aliquots each, were used as controls. To validate the multiplexed results, we used single-target ELISA assays to measure the proteins with the largest serum concentration changes after surgery in sera collected pre- and post-surgically from the previous five patients and 10 additional patients. Results: The multiplexed array revealed nine proteins with more than two-fold post-surgical decrease in at least two of five patients. However, validation using single ELISAs showed that only two proteins tested displayed more than two-fold post-surgical decrease in one of the five original patients. In the independent cohort, six of the proteins tested showed at least a two-fold decrease post-surgery in at least one patient. Conclusions: Our study found that the Quantibody® Human Kiloplex Array results could not be reliably replicated with individual ELISA assays and most hits would likely represent false positives if applied to biomarker discovery. These findings suggest that data from novel, high-throughput proteomic platforms need stringent validation to avoid false discoveries.
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Affiliation(s)
- Annie He Ren
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
- Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Ioannis Prassas
- Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Antoninus Soosaipillai
- Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Stephanie Jarvi
- Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Steven Gallinger
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
- Pancreatic Surgical Oncology Program, University Health Network, Canada, Toronto, Ontario, Canada
| | - Vathany Kulasingam
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
- Department of Clinical Biochemistry, University Health Network, Toronto, Ontario, Canada
| | - Eleftherios P. Diamandis
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
- Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
- Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada
- Department of Clinical Biochemistry, University Health Network, Toronto, Ontario, Canada
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21
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Ren AH, Prassas I, Soosaipillai A, Jarvi S, Gallinger S, Kulasingam V, Diamandis EP. Investigating a novel multiplex proteomics technology for detection of changes in serum protein concentrations that may correlate to tumor burden. F1000Res 2020; 9:732. [PMID: 33274048 PMCID: PMC7682495 DOI: 10.12688/f1000research.24654.1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/22/2020] [Indexed: 03/31/2024] Open
Abstract
Background: To account for cancer heterogeneity, we previously introduced the concept of "personalized" tumor markers, which are biomarkers that are informative in subsets of patients or even a single patient. Recent developments in various multiplex protein technologies create excitement for the discovery of markers of tumor burden in individual patients, but the reliability of the technologies remains to be tested for this purpose. Here, we sought to explore the potential of a novel proteomics platform, which utilizes a multiplexed antibody microarray, to detect changes in serum protein concentration that may correlate to tumor burden in pancreatic cancer. Methods: We applied the Quantibody® Human Kiloplex Array to simultaneously measure 1,000 proteins in sera obtained pre- and post-surgically from five pancreatic cancer patients. We expected that proteins which decreased post-surgery may correlate to tumor burden. Sera from two healthy individuals, split into two aliquots each, were used as controls. To validate the multiplexed results, we used single-target ELISA assays to measure the proteins with the largest serum concentration changes after surgery in sera collected pre- and post-surgically from the previous five patients and 10 additional patients. Results: The multiplexed array revealed nine proteins with more than two-fold post-surgical decrease in at least two of five patients. However, validation using single ELISAs showed that only two proteins tested displayed more than two-fold post-surgical decrease in one of the five original patients. In the independent cohort, six of the proteins tested showed at least a two-fold decrease post-surgery in at least one patient. Conclusions: Our study found that the Quantibody® Human Kiloplex Array results could not be reliably replicated with individual ELISA assays and most hits would likely represent false positives if applied to biomarker discovery. These findings suggest that data from novel, high-throughput proteomic platforms need stringent validation to avoid false discoveries.
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Affiliation(s)
- Annie He Ren
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
- Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Ioannis Prassas
- Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Antoninus Soosaipillai
- Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Stephanie Jarvi
- Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Steven Gallinger
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
- Pancreatic Surgical Oncology Program, University Health Network, Canada, Toronto, Ontario, Canada
| | - Vathany Kulasingam
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
- Department of Clinical Biochemistry, University Health Network, Toronto, Ontario, Canada
| | - Eleftherios P. Diamandis
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
- Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
- Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada
- Department of Clinical Biochemistry, University Health Network, Toronto, Ontario, Canada
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Zhang X, Shi X, Lu X, Li Y, Zhan C, Akhtar ML, Yang L, Bai Y, Zhao J, Wang Y, Yao Y, Li Y, Nie H. Novel Metabolomics Serum Biomarkers for Pancreatic Ductal Adenocarcinoma by the Comparison of Pre-, Postoperative and Normal Samples. J Cancer 2020; 11:4641-4651. [PMID: 32626510 PMCID: PMC7330680 DOI: 10.7150/jca.41250] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Accepted: 04/14/2020] [Indexed: 12/11/2022] Open
Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive human malignancies. The metabolomic approaches are developed to discover the novel biomarkers of PDAC. Methods: 550 preoperative, postoperative PDAC and normal controls (NCs) serums were employed to characterize metabolic alterations in training and validation sets by LC-MS. Results: The results of PLS-DA analysis indicated that three groups could be distinguished clearly and the post-PDAC group is adjacent to a normal group as compared with pre-PDAC group. Further results showed that histidinyl-lysine significantly increased whereas docosahexaenoic acid and LysoPC (14:0) decreased in pre-PDAC patients as compared with NCs. And these three markers had a significant tendency to recover after tumor resection. The validation set results revealed that for CA19-9 negative patients, 92.3% (12/13) of them can be screened using these three metabolites. The combination of these markers could significantly improve the diagnostic performance for PDAC, with higher sensitivity (0.93), specificity (0.92) and AUC (0.97). Moreover, network and pathways analyses explored the latent relationship among differential metabolites. The glycerolipid metabolism and primary bile acid synthesis showed variation in network and pathway analysis. Conclusions: These three markers combined with CA199 displayed high sensitivity and specificity for detecting PDAC patients from NCs. The results indicated that these three metabolites could be regarded as potential biomarkers to distinguish PDAC from NCs.
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Affiliation(s)
- Xiaohan Zhang
- School of Life Science and Technology, Harbin Institute of Technology, Harbin, China
| | - Xiuyun Shi
- School of Life Science and Technology, Harbin Institute of Technology, Harbin, China
| | - Xin Lu
- School of Life Science and Technology, Harbin Institute of Technology, Harbin, China
| | - Yiqun Li
- School of Life Science and Technology, Harbin Institute of Technology, Harbin, China
| | - Chao Zhan
- The Affiliated Tumor Hospital, Harbin Medical University, Harbin, China
| | | | - Lijun Yang
- School of Life Science and Technology, Harbin Institute of Technology, Harbin, China
| | - Yunfan Bai
- School of Life Science and Technology, Harbin Institute of Technology, Harbin, China
| | - Jianxiang Zhao
- School of Life Science and Technology, Harbin Institute of Technology, Harbin, China
| | - Yu Wang
- School of Life Science and Technology, Harbin Institute of Technology, Harbin, China
| | - Yuanfei Yao
- The Affiliated Tumor Hospital, Harbin Medical University, Harbin, China
| | - Yu Li
- School of Life Science and Technology, Harbin Institute of Technology, Harbin, China
| | - Huan Nie
- School of Life Science and Technology, Harbin Institute of Technology, Harbin, China
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23
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Da Z, Gao L, Su G, Yao J, Fu W, Zhang J, Zhang X, Pei Z, Yue P, Bai B, Lin Y, Meng W, Li X. Bioinformatics combined with quantitative proteomics analyses and identification of potential biomarkers in cholangiocarcinoma. Cancer Cell Int 2020; 20:130. [PMID: 32336950 PMCID: PMC7178764 DOI: 10.1186/s12935-020-01212-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Accepted: 04/15/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Cholangiocarcinoma (CCA) is an invasive malignancy arising from biliary epithelial cells; it is the most common primary tumour of the bile tract and has a poor prognosis. The aim of this study was to screen prognostic biomarkers for CCA by integrated multiomics analysis. METHODS The GSE32225 dataset was derived from the Gene Expression Omnibus (GEO) database and comprehensively analysed by using R software and The Cancer Genome Atlas (TCGA) database to obtain the differentially expressed RNAs (DERNAs) associated with CCA prognosis. Quantitative isobaric tags for relative and absolute quantification (iTRAQ) proteomics was used to screen differentially expressed proteins (DEPs) between CCA and nontumour tissues. Through integrated analysis of DERNA and DEP data, we obtained candidate proteins APOF, ITGAV and CASK, and immunohistochemistry was used to detect the expression of these proteins in CCA. The relationship between CASK expression and CCA prognosis was further analysed. RESULTS Through bioinformatics analysis, 875 DERNAs were identified, of which 10 were associated with the prognosis of the CCA patients. A total of 487 DEPs were obtained by using the iTRAQ technique. Comprehensive analysis of multiomics data showed that CASK, ITGAV and APOF expression at both the mRNA and protein levels were different in CCA compared with nontumour tissues. CASK was found to be expressed in the cytoplasm and nucleus of CCA cells in 38 (45%) of 84 patients with CCA. Our results suggested that patients with positive CASK expression had significantly better overall survival (OS) and recurrence-free survival (RFS) than those with negative CASK expression. Univariate and multivariate analyses demonstrated that negative expression of CASK was a significantly independent risk factor for OS and RFS in CCA patients. CONCLUSIONS CASK may be a tumour suppressor; its low expression is an independent risk factor for a poor prognosis in CCA patients, and so it could be used as a clinically valuable prognostic marker.
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Affiliation(s)
- Zijian Da
- The First Clinical Medical College, Lanzhou University, Lanzhou, 730000 China
| | - Long Gao
- The First Clinical Medical College, Lanzhou University, Lanzhou, 730000 China
| | - Gang Su
- Institute of Genetics, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000 China
| | - Jia Yao
- The First Clinical Medical College, Lanzhou University, Lanzhou, 730000 China
- Division of Scientific Research and Development Planning, The First Hospital of Lanzhou University, Lanzhou, 730000 China
| | - Wenkang Fu
- The First Clinical Medical College, Lanzhou University, Lanzhou, 730000 China
| | - Jinduo Zhang
- Department of Special Minimally Invasive Surgery, The First Hospital of Lanzhou University, Lanzhou, 730000 China
- Gansu Province Institute of Hepatopancreatobiliary, Lanzhou, 730000 China
- Gansu Province Key Laboratory Biotherapy and Regenerative Medicine, Lanzhou, 730000 China
| | - Xu Zhang
- The First Clinical Medical College, Lanzhou University, Lanzhou, 730000 China
| | - Zhaoji Pei
- The First Clinical Medical College, Lanzhou University, Lanzhou, 730000 China
| | - Ping Yue
- Department of Special Minimally Invasive Surgery, The First Hospital of Lanzhou University, Lanzhou, 730000 China
- Gansu Province Institute of Hepatopancreatobiliary, Lanzhou, 730000 China
- Gansu Province Key Laboratory Biotherapy and Regenerative Medicine, Lanzhou, 730000 China
| | - Bing Bai
- Department of Special Minimally Invasive Surgery, The First Hospital of Lanzhou University, Lanzhou, 730000 China
- Gansu Province Institute of Hepatopancreatobiliary, Lanzhou, 730000 China
- Gansu Province Key Laboratory Biotherapy and Regenerative Medicine, Lanzhou, 730000 China
| | - Yanyan Lin
- Department of Special Minimally Invasive Surgery, The First Hospital of Lanzhou University, Lanzhou, 730000 China
- Gansu Province Institute of Hepatopancreatobiliary, Lanzhou, 730000 China
- Gansu Province Key Laboratory Biotherapy and Regenerative Medicine, Lanzhou, 730000 China
| | - Wenbo Meng
- The First Clinical Medical College, Lanzhou University, Lanzhou, 730000 China
- Department of Special Minimally Invasive Surgery, The First Hospital of Lanzhou University, Lanzhou, 730000 China
- Division of Scientific Research and Development Planning, The First Hospital of Lanzhou University, Lanzhou, 730000 China
- Institute of Genetics, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000 China
- Gansu Province Institute of Hepatopancreatobiliary, Lanzhou, 730000 China
- Gansu Province Key Laboratory Biotherapy and Regenerative Medicine, Lanzhou, 730000 China
| | - Xun Li
- The First Clinical Medical College, Lanzhou University, Lanzhou, 730000 China
- Gansu Province Institute of Hepatopancreatobiliary, Lanzhou, 730000 China
- Gansu Province Key Laboratory Biotherapy and Regenerative Medicine, Lanzhou, 730000 China
- The Second Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, 730000 China
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Zhu Y, Zhang H, Chen N, Hao J, Jin H, Ma X. Diagnostic value of various liquid biopsy methods for pancreatic cancer: A systematic review and meta-analysis. Medicine (Baltimore) 2020; 99:e18581. [PMID: 32011436 PMCID: PMC7220382 DOI: 10.1097/md.0000000000018581] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Liquid biopsy is a novel method for cancer diagnosis, which has been applied in lung and breast cancers, demonstrating high diagnostic value. However, clinical value of it in pancreatic cancer (PC) remains to be verified. The aim of this meta-analysis was to evaluate overall diagnostic value of various liquid biopsy methods (circulating tumor DNA, circulating tumor cells and exosomes) in detecting PC. METHODS We comprehensively searched relevant studies in PubMed, Medline, Embase, and Web of Science without time limitation according to PRISMA. Data necessary for reconstructing a 2 × 2 table was calculated from the original articles. The methodological quality of included studies was evaluated by QUADAS-2. Statistical analysis including was performed by the software Meta-Disc version 1.4, and STATA 14.2. RESULTS A total of 19 studies including 1872 individuals were included in this meta-analysis. In which, 7 were studies about ctDNA, 7 were on CTCs and 6 were about exosomes (Sefrioui D, studied diagnostic accuracy of both ctDNA and CTCs, with no common patients in these 2 groups). The pooled sensitivity estimates for ctDNA, CTCs and exosomes in detecting PC with their 95% confidential intervals (95% CI) were 0.64 (95%CI 0.58-0.70), 0.74 (95%CI 0.68-0.79) and 0.93 (95%CI 0.90-0.95), respectively. The pooled specificity estimates were 0.92(95%CI 0.88-0.95), 0.83 (95%CI 0.78-0.88) and 0.92 (95%CI 0.88-0.95), respectively. The area under curve (AUC) of the sROC for ctDNA, CTCs and exosomes in detecting PC were 0.9478, 0.8166, and 0.9819, respectively. The overall sensitivity, specificity and AUC of the sROC curve for overall liquid biopsy in detecting PC were 0.80 (95%CI 0.77-0.82), 0.89 (95%CI 0.87-0.91) and 0.9478, respectively. CONCLUSION This meta-analysis confirmed that liquid biopsy had high diagnostic value in detecting PC. In ctDNA, CTCs and exosomes these 3 subgroups, exosomes showed highest sensitivity and specificity.
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Affiliation(s)
- Yuzhou Zhu
- Department of Biotherapy, Cancer Center
- Department of Gastrointestinal Surgery
| | - Hao Zhang
- Department of Pancreatic Surgery, West China Hospital, Sichuan University
| | | | | | | | - Xuelei Ma
- Department of Biotherapy, Cancer Center
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
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25
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Moore HB, Culp-Hill R, Reisz JA, Lawson PJ, Sauaia A, Schulick RD, Del Chiaro M, Nydam TL, Moore EE, Hansen KC, D'Alessandro A. The metabolic time line of pancreatic cancer: Opportunities to improve early detection of adenocarcinoma. Am J Surg 2019; 218:1206-1212. [PMID: 31514959 DOI: 10.1016/j.amjsurg.2019.08.015] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2019] [Revised: 06/30/2019] [Accepted: 08/20/2019] [Indexed: 12/24/2022]
Abstract
BACKGROUND A reliable biomarker to detect pancreatic ductal adenocarcinoma (PDAC) continues to be elusive. With employing metabolomics we hypothesize that a broader analysis of systemic blood can differentiate different stages of PDAC. METHODS Patients undergoing pancreatic resection had plasma samples grouped by diagnosis and assayed with mass spectrometry. 10 per group [neuroendocrine (PNET), intraductal papillary mucinous neoplasm (IPMN), localized PDAC, locally advanced PDAC, and metastatic] were analyzed to assess if metabolites could delineation different stages of adenocarcinoma. RESULTS Of the 215 metabolites measured, four had a stronger correlation to disease burden than CA19-9. However, none of these metabolites differentiated stepwise progression in malignancy. Principal component analysis identified five metabolic components. Each cancer cohort was characterized by a unique combination of components, two components were predictors of PDCA stages. CONCLUSIONS Enhanced metabolomic analysis identified metabolic pathways that may assist in differentiating PDCA stages that do not occur in a linear stepwise progression.
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Affiliation(s)
| | - Rachel Culp-Hill
- Department of Biochemistry and Molecular Genetics, University of Colorado, USA
| | - Julia A Reisz
- Department of Biochemistry and Molecular Genetics, University of Colorado, USA
| | | | - Angela Sauaia
- School of Public Health, University of Colorado, USA
| | | | | | | | - Ernest E Moore
- Department of Surgery, Denver Health Medical Center, USA
| | - Kirk C Hansen
- Department of Biochemistry and Molecular Genetics, University of Colorado, USA
| | - Angelo D'Alessandro
- Department of Biochemistry and Molecular Genetics, University of Colorado, USA
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Qian L, Li Q, Baryeh K, Qiu W, Li K, Zhang J, Yu Q, Xu D, Liu W, Brand RE, Zhang X, Chen W, Liu G. Biosensors for early diagnosis of pancreatic cancer: a review. Transl Res 2019; 213:67-89. [PMID: 31442419 DOI: 10.1016/j.trsl.2019.08.002] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Revised: 08/06/2019] [Accepted: 08/06/2019] [Indexed: 12/21/2022]
Abstract
Pancreatic cancer is characterized by extremely high mortality and poor prognosis and is projected to be the leading cause of cancer deaths by 2030. Due to the lack of early symptoms and appropriate methods to detect pancreatic carcinoma at an early stage as well as its aggressive progression, the disease is often quite advanced by the time a definite diagnosis is established. The 5-year relative survival rate for all stages is approximately 8%. Therefore, detection of pancreatic cancer at an early surgically resectable stage is the key to decrease mortality and to improve survival. The traditional methods for diagnosing pancreatic cancer involve an imaging test, such as ultrasound or magnetic resonance imaging, paired with a biopsy of the mass in question. These methods are often expensive, time consuming, and require trained professionals to use the instruments and analyze the imaging. To overcome these issues, biosensors have been proposed as a promising tool for the early diagnosis of pancreatic cancer. The present review critically discusses the latest developments in biosensors for the early diagnosis of pancreatic cancer. Protein and microRNA biomarkers of pancreatic cancer and corresponding biosensors for pancreatic cancer diagnosis have been reviewed, and all these cases demonstrate that the emerging biosensors are becoming an increasingly relevant alternative to traditional techniques. In addition, we discuss the existing problems in biosensors and future challenges.
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Affiliation(s)
- Lisheng Qian
- Institute of Biomedical and Health, School of Life and Health Science, Anhui Science and Technology University, Fengyang, Anhui, PR China
| | - Qiaobin Li
- Department of Chemistry & Biochemistry, North Dakota State University, Fargo, North Dakota
| | - Kwaku Baryeh
- Department of Chemistry & Biochemistry, North Dakota State University, Fargo, North Dakota
| | - Wanwei Qiu
- Institute of Biomedical and Health, School of Life and Health Science, Anhui Science and Technology University, Fengyang, Anhui, PR China
| | - Kun Li
- Institute of Biomedical and Health, School of Life and Health Science, Anhui Science and Technology University, Fengyang, Anhui, PR China
| | - Jing Zhang
- Institute of Biomedical and Health, School of Life and Health Science, Anhui Science and Technology University, Fengyang, Anhui, PR China
| | - Qingcai Yu
- Institute of Biomedical and Health, School of Life and Health Science, Anhui Science and Technology University, Fengyang, Anhui, PR China
| | - Dongqin Xu
- Institute of Biomedical and Health, School of Life and Health Science, Anhui Science and Technology University, Fengyang, Anhui, PR China
| | - Wenju Liu
- Institute of Biomedical and Health, School of Life and Health Science, Anhui Science and Technology University, Fengyang, Anhui, PR China
| | - Randall E Brand
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Xueji Zhang
- Institute of Biomedical and Health, School of Life and Health Science, Anhui Science and Technology University, Fengyang, Anhui, PR China; School of Biomedical Engineering, Shenzhen University Health Science Center, Shenzhen, Guangdong, PR China.
| | - Wei Chen
- Institute of Biomedical and Health, School of Life and Health Science, Anhui Science and Technology University, Fengyang, Anhui, PR China; School of Food Science & Engineering, Hefei University of Technology, Hefei, Anhui, PR China.
| | - Guodong Liu
- Institute of Biomedical and Health, School of Life and Health Science, Anhui Science and Technology University, Fengyang, Anhui, PR China; Department of Chemistry & Biochemistry, North Dakota State University, Fargo, North Dakota.
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27
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Luchini C, Veronese N, Nottegar A, Cappelletti V, Daidone MG, Smith L, Parris C, Brosens LAA, Caruso MG, Cheng L, Wolfgang CL, Wood LD, Milella M, Salvia R, Scarpa A. Liquid Biopsy as Surrogate for Tissue for Molecular Profiling in Pancreatic Cancer: A Meta-Analysis Towards Precision Medicine. Cancers (Basel) 2019; 11:1152. [PMID: 31405192 PMCID: PMC6721631 DOI: 10.3390/cancers11081152] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2019] [Revised: 08/05/2019] [Accepted: 08/07/2019] [Indexed: 12/24/2022] Open
Abstract
Liquid biopsy (LB) is a non-invasive approach representing a promising tool for new precision medicine strategies for cancer treatment. However, a comprehensive analysis of its reliability for pancreatic cancer (PC) is lacking. To this aim, we performed the first meta-analysis on this topic. We calculated the pooled sensitivity, specificity, positive (LR+) and negative (LR-) likelihood ratio, and diagnostic odds ratio (DOR). A summary receiver operating characteristic curve (SROC) and area under curve (AUC) were used to evaluate the overall accuracy. We finally assessed the concordance rate of all mutations detected by multi-genes panels. Fourteen eligible studies involving 369 patients were included. The overall pooled sensitivity and specificity were 0.70 and 0.86, respectively. The LR+ was 3.85, the LR- was 0.34 and DOR was 15.84. The SROC curve with an AUC of 0.88 indicated a relatively high accuracy of LB for molecular characterization of PC. The concordance rate of all mutations detected by multi-genes panels was 31.9%. LB can serve as surrogate for tissue in the molecular profiling of PC, because of its relatively high sensitivity, specificity and accuracy. It represents a unique opportunity to be further explored towards its introduction in clinical practice and for developing new precision medicine approaches against PC.
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Affiliation(s)
- Claudio Luchini
- Department of Diagnostics and Public Health, Section of Pathology, University of Verona, 37134 Verona, Italy
| | - Nicola Veronese
- National Institute of Gastroenterology-Research Hospital, IRCCS "S. de Bellis", Castellana Grotte, 70013 Bari, Italy
| | - Alessia Nottegar
- Department of Surgery, Section of Pathology, San Bortolo Hospital, 36100 Vicenza, Italy
| | - Vera Cappelletti
- Applied Research and Technological Development Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, 20133 Milano, Italy
| | - Maria G Daidone
- Applied Research and Technological Development Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, 20133 Milano, Italy
| | - Lee Smith
- Faculty of Science and Engineering, Anglia Ruskin University, Cambridge CB1 1PT, UK
| | - Christopher Parris
- Faculty of Science and Engineering, Anglia Ruskin University, Cambridge CB1 1PT, UK
| | - Lodewijk A A Brosens
- Department of Diagnostics and Public Health, Section of Pathology, University of Verona, 37134 Verona, Italy
- Department of Pathology, University Medical Center Utrecht, Utrecht University, 3584CX Utrecht, The Netherlands
- Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6526GA Nijmegen, The Netherlands
| | - Maria G Caruso
- National Institute of Gastroenterology-Research Hospital, IRCCS "S. de Bellis", Castellana Grotte, 70013 Bari, Italy
| | - Liang Cheng
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Christopher L Wolfgang
- Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21211, USA
| | - Laura D Wood
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21211, USA
- Department of Oncology, Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21211, USA
| | - Michele Milella
- Department of Medicine, Section of Medical Oncology, University and Hospital Trust of Verona, 37134 Verona, Italy
| | - Roberto Salvia
- Department of General and Visceral Surgery, The Pancreas Institute, University and Hospital Trust of Verona, 37134 Verona, Italy
| | - Aldo Scarpa
- Department of Diagnostics and Public Health, Section of Pathology, University of Verona, 37134 Verona, Italy.
- ARC-Net Research Center, University of Verona, 37134 Verona, Italy.
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28
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Haznadar M, Diehl CM, Parker AL, Krausz KW, Bowman ED, Rabibhadana S, Forgues M, Bhudhisawasdi V, Gonzalez FJ, Mahidol C, Budhu A, Wang XW, Ruchirawat M, Harris CC. Urinary Metabolites Diagnostic and Prognostic of Intrahepatic Cholangiocarcinoma. Cancer Epidemiol Biomarkers Prev 2019; 28:1704-1711. [PMID: 31358519 DOI: 10.1158/1055-9965.epi-19-0453] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2019] [Revised: 06/06/2019] [Accepted: 07/23/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Liver cancer is the second leading cause of cancer-related deaths worldwide. With a predicted 2.4-fold rise in liver cancer incidence by 2020, there is an urgent need for early, inexpensive diagnostic biomarkers to deploy in the clinic. METHODS We employed ultraperformance liquid chromatography tandem mass-spectrometry (UPLC/MS-MS) for the quantitation of four metabolites, creatine riboside (CR), N-acetylneuraminic acid (NANA), cortisol sulfate, and a lipid molecule designated as 561+, in urine samples from the NCI-MD cohort comprising 98 hepatocellular carcinoma (HCC) cases, 101 high-risk subjects, and 95 controls. Validation was carried out in the TIGER-LC cohort [n = 370 HCC and intrahepatic cholangiocarcinoma (ICC) cases, 471 high-risk subjects, 251 controls], where ICC, the second most common primary hepatic malignancy, is highly prevalent. Metabolite quantitation was also conducted in TIGER-LC tissue samples (n = 48 ICC; n = 51 HCC). RESULTS All profiled metabolites were significantly increased in liver cancer when compared with high-risk subjects and controls in the NCI-MD study. In the TIGER-LC cohort, the four-metabolite profile was superior at classifying ICC than a clinically utilized marker, CA19-9, and their combination led to a significantly improved model (AUC = 0.88, P = 4E-8). Metabolites CR and NANA were significantly elevated in ICC when compared with HCC cases in both urine and tissue samples. High levels of CR were associated with poorer prognosis in ICC. CONCLUSIONS Four metabolites are significantly increased in HCC and ICC and are robust at classifying ICC in combination with the clinically utilized marker CA19-9. IMPACT Noninvasive urinary metabolite biomarkers hold promise for diagnostic and prognostic evaluation of ICC.
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Affiliation(s)
- Majda Haznadar
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
| | - Christopher M Diehl
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
| | - Amelia L Parker
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
| | - Kristopher W Krausz
- Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
| | - Elise D Bowman
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
| | - Siritida Rabibhadana
- Laboratory of Chemical Carcinogenesis, Chulabhorn Research Institute, Bangkok, Thailand
| | - Marshonna Forgues
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
| | | | - Frank J Gonzalez
- Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
| | - Chulabhorn Mahidol
- Laboratory of Chemical Carcinogenesis, Chulabhorn Research Institute, Bangkok, Thailand.,Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Bangkok, Thailand
| | - Anuradha Budhu
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
| | - Xin W Wang
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
| | - Mathuros Ruchirawat
- Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Bangkok, Thailand.,Center of Excellence on Environmental Health and Toxicology, Office of Higher Education Commission, Ministry of Education, Bangkok, Thailand
| | - Curtis C Harris
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
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29
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Kim K, Yoo D, Lee HS, Lee KJ, Park SB, Kim C, Jo JH, Jung DE, Song SY. Identification of potential biomarkers for diagnosis of pancreatic and biliary tract cancers by sequencing of serum microRNAs. BMC Med Genomics 2019; 12:62. [PMID: 31096984 PMCID: PMC6524273 DOI: 10.1186/s12920-019-0521-8] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Accepted: 05/07/2019] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Pancreatic and biliary tract cancer (PC and BTC, respectively) are difficult to diagnose because of their clinical characteristics; however, recent studies suggest that serum microRNAs (miRNAs) might be the key to developing more efficient diagnostic methods for these cancers. METHODS We analysed the genome-wide expression of serum miRNAs in PC and BTC patients to identify novel biomarker candidates using high-throughput sequencing and experimentally validated miRNAs on clinical samples. RESULTS Statistical and classification analysis of the serum miRNA-expression profiles of 55 patient samples showed distinguishable patterns between cancer patients and healthy controls; however, we were unable to distinguish the two cancers. We found that three of the highest performing miRNAs were capable of distinguishing cancer patients from controls, with an accuracy of 92.7%. Additionally, dysregulation of these three cancer-specific miRNAs was demonstrated in an independent sample group by quantitative reverse transcription polymerase chain reaction. CONCLUSIONS These results suggested three candidate serum miRNAs (mir-744-5p, mir-409-3p, and mir-128-3p) as potential biomarkers for PC and BTC diagnosis.
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Affiliation(s)
- Kwondo Kim
- Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, Republic of Korea
- C&K genomics, C-1008, H businesspark, 26, Beobwon-ro 9-gil, Songpa-gu, Seoul, Republic of Korea
| | - DongAhn Yoo
- Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, Republic of Korea
- C&K genomics, C-1008, H businesspark, 26, Beobwon-ro 9-gil, Songpa-gu, Seoul, Republic of Korea
| | - Hee Seung Lee
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea
| | - Kyong Joo Lee
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea
| | - Soo Been Park
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea
| | - Chanyang Kim
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea
| | - Jung Hyun Jo
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea
- Division of Gastroenterology, Department of Internal Medicine, Hallym University Hangang Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea
| | - Dawoon E. Jung
- Institute of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea
| | - Si Young Song
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea
- Institute of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea
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30
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Husi H, Fernandes M, Skipworth RJ, Miller J, Cronshaw AD, Fearon KCH, Ross JA. Identification of diagnostic upper gastrointestinal cancer tissue type-specific urinary biomarkers. Biomed Rep 2019; 10:165-174. [PMID: 30906545 PMCID: PMC6423495 DOI: 10.3892/br.2019.1190] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Accepted: 01/02/2019] [Indexed: 02/07/2023] Open
Abstract
Several potential urinary biomarkers exhibiting an association with upper gastrointestinal tumour growth have been previously identified, of which S100A6, S100A9, rabenosyn-5 and programmed cell death 6-interacting protein (PDCD6IP) were further validated and found to be upregulated in malignant tumours. The cancer cohort from our previous study was subclassified to assess whether distinct molecular markers can be identified for each individual cancer type using a similar approach. Urine samples from patients with cancers of the stomach, oesophagus, oesophagogastric junction or pancreas were analysed by surface-enhanced laser desorption/ionization-time-of-flight mass spectrometry using both CM10 and IMAC30 (Cu2+-complexed) chip types and LC-MS/MS-based mass spectrometry after chromatographic enrichment. This was followed by protein identification, pattern matching and validation by western blotting. We found 8 m/z peaks with statistical significance for the four cancer types investigated, of which m/z 2447 and 2577 were identified by pattern matching as fragments of cathepsin-B (CTSB) and cystatin-B (CSTB); both molecules are indicative of pancreatic cancer. Additionally, we observed a potential association of upregulated α-1-antichymotrypsin with pancreatic and gastric cancers, of PDCD6IP, vitelline membrane outer layer protein 1 homolog (VMO1) and triosephosphate isomerase (TPI1) with oesophagogastric junctional cancers, and of complement C4-A, prostatic acid phosphatase, azurocidin and histone-H1 with oesophageal cancer. Furthermore, the potential pancreatic cancer biomarkers CSTB and CTSB were validated independently by western blotting. Therefore, the present study identified two new potential urinary biomarkers that appear to be associated with pancreatic cancer. This may provide a simple, non-invasive screening test for use in the clinical setting.
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Affiliation(s)
- Holger Husi
- Department of Diabetes and Cardiovascular Science, University of the Highlands and Islands, Inverness IV2 3JH, UK.,BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8TA, UK.,School of Clinical Sciences and Community Health, University of Edinburgh, Edinburgh EH16 4SB, UK
| | - Marco Fernandes
- BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8TA, UK
| | - Richard J Skipworth
- School of Clinical Sciences and Community Health, University of Edinburgh, Edinburgh EH16 4SB, UK
| | - Janice Miller
- School of Clinical Sciences and Community Health, University of Edinburgh, Edinburgh EH16 4SB, UK
| | - Andrew D Cronshaw
- School of Biological Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK
| | - Kenneth C H Fearon
- School of Clinical Sciences and Community Health, University of Edinburgh, Edinburgh EH16 4SB, UK
| | - James A Ross
- School of Clinical Sciences and Community Health, University of Edinburgh, Edinburgh EH16 4SB, UK
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31
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Corral JE, Mareth KF, Riegert-Johnson DL, Das A, Wallace MB. Diagnostic Yield From Screening Asymptomatic Individuals at High Risk for Pancreatic Cancer: A Meta-analysis of Cohort Studies. Clin Gastroenterol Hepatol 2019; 17:41-53. [PMID: 29775792 DOI: 10.1016/j.cgh.2018.04.065] [Citation(s) in RCA: 74] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2018] [Revised: 04/24/2018] [Accepted: 04/29/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS There have been few studies of abdominal imaging screening of individuals at high risk for pancreatic cancer (based on family history or genetic variants). We performed a meta-analysis of prospective cohort studies to determine the diagnostic yield and outcomes of abdominal imaging screening for asymptomatic individuals at high risk. METHODS Through a systematic review of multiple electronic databases and conference proceedings through July 2017, we identified prospective cohort studies (>20 patients) of asymptomatic adults determined to be at high-risk of pancreatic cancer (lifetime risk >5%, including specific genetic-associated conditions) who were screened by endoscopic ultrasound (EUS) and/or magnetic resonance imaging (MRI) to detect pancreatic lesions. Our primary outcome was identification of high-risk pancreatic lesions (high-grade pancreatic intraepithelial neoplasia, high-grade dysplasia, or adenocarcinoma) at initial screening, and overall incidence during follow up. Summary estimates were reported as incidence rates per 100 patient-years. RESULTS We identified 19 studies comprising 7085 individuals at high risk for pancreatic cancer; of these, 1660 patients were evaluated by EUS and/or MRI. Fifty-nine high-risk lesions were identified (43 adenocarcinomas: 28 during the initial exam and 15 during follow-up surveillance) and 257 patients underwent pancreatic surgery. Based on our meta-analysis, the overall diagnostic yield screening for high-risk pancreatic lesions was 0.74 (95% CI, 0.33-1.14), with moderate heterogeneity among studies. The number needed to screen to identify 1 patient with a high-risk lesion was 135 (95% CI, 88-303). The diagnostic yield was similar for patients with different genetic features that increased risk, and whether patients were screened by EUS or MRI. CONCLUSIONS Based on meta-analysis, 135 patients at high-risk for pancreatic cancer must be screened to identify 1 patient with a high-risk pancreatic lesion. Further studies are needed to determine whether screening reduces mortality and is cost effectiveness for individuals at high-risk of pancreatic cancer.
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Affiliation(s)
- Juan E Corral
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida
| | - Karl F Mareth
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida
| | | | - Ananya Das
- Center for Digestive Health, St. Joseph's Hospital and Medical Center, Phoenix, Arizona
| | - Michael B Wallace
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida.
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32
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Tsen A, Barbara M, Rosenkranz L. Dilemma of elevated CA 19-9 in biliary pathology. Pancreatology 2018; 18:862-867. [PMID: 30249386 DOI: 10.1016/j.pan.2018.09.004] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Revised: 09/13/2018] [Accepted: 09/18/2018] [Indexed: 12/11/2022]
Abstract
Carbohydrate antigen 19-9 (CA 19-9) is a tumor marker which has been extensively evaluated and widely utilized primarily in diagnosing and prognosticating pancreaticobiliary malignancies. Levels may be significantly influenced and elevated in cases of benign biliary conditions however, especially in obstructive jaundice, thereby posing difficulty in distinguishing between benign and malignant cholestasis. A myriad of studies have focused on elucidating proper use and interpretation of CA 19-9 in pancreatic cancer as well as in the setting of cholestasis. These studies have demonstrated that many factors influence CA 19-9 values and various methods for interpreting CA 19-9 in obstructive jaundice have been proposed. With improvements in diagnostic imaging, advancements in endoscopic modalities, and likelihood that management will not change based on the results of the test, clinicians should be cautious when ordering CA 19-9 and consider the reasons for measuring the tumor marker.
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Affiliation(s)
- Adrianne Tsen
- University of Texas Health Science Center at San Antonio, 5623 Hamilton Wolfe, #712, San Antonio, TX 78240, USA.
| | - Mary Barbara
- Department of Internal Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
| | - Laura Rosenkranz
- Department of Gastroenterology and Advanced Therapeutic Endoscopy, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
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33
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Broadhurst PJ, Hart AR. Metformin as an Adjunctive Therapy for Pancreatic Cancer: A Review of the Literature on Its Potential Therapeutic Use. Dig Dis Sci 2018; 63:2840-2852. [PMID: 30159732 DOI: 10.1007/s10620-018-5233-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2018] [Accepted: 07/31/2018] [Indexed: 12/11/2022]
Abstract
Pancreatic ductal adenocarcinoma has the worst prognosis of any cancer. New adjuvant chemotherapies are urgently required, which are well tolerated by patients with unresectable cancers. This paper reviews the existing proof of concept data, namely laboratory, pharmacoepidemiological, experimental medicine and clinical trial evidence for investigating metformin in patients with pancreatic ductal adenocarcinoma. Laboratory evidence shows metformin inhibits mitochondrial ATP synthesis which directly and indirectly inhibits carcinogenesis. Drug-drug interactions of metformin with proton pump inhibitors and histamine H2-receptor antagonists may be of clinical relevance and pertinent to future research of metformin in pancreatic ductal adenocarcinoma. To date, most cohort studies have demonstrated a positive association with metformin on survival in pancreatic ductal adenocarcinoma, although there are many methodological limitations with such study designs. From experimental medicine studies, there are sparse data in humans. The current trials of metformin have methodological limitations. Two small randomized controlled trials (RCTs) reported null findings, but there were potential inequalities in cancer staging between groups and poor compliance with the intervention. Proof of concept data, predominantly from laboratory work, supports assessing metformin as an adjunct for pancreatic ductal adenocarcinoma in RCTs. Ideally, more experimental medicine studies are needed for proof of concept. However, many feasibility criteria need to be answered before such trials can progress.
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Affiliation(s)
| | - Andrew R Hart
- Norwich Medical School, University of East Anglia, Norwich, NR4 7TJ, UK.,Norfolk and Norwich University Hospital NHS Trust, University of East Anglia, Norwich, NR4 7TJ, UK
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34
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Long NP, Yoon SJ, Anh NH, Nghi TD, Lim DK, Hong YJ, Hong SS, Kwon SW. A systematic review on metabolomics-based diagnostic biomarker discovery and validation in pancreatic cancer. Metabolomics 2018; 14:109. [PMID: 30830397 DOI: 10.1007/s11306-018-1404-2] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2018] [Accepted: 07/31/2018] [Indexed: 12/26/2022]
Abstract
INTRODUCTION Metabolomics is an emerging approach for early detection of cancer. Along with the development of metabolomics, high-throughput technologies and statistical learning, the integration of multiple biomarkers has significantly improved clinical diagnosis and management for patients. OBJECTIVES In this study, we conducted a systematic review to examine recent advancements in the oncometabolomics-based diagnostic biomarker discovery and validation in pancreatic cancer. METHODS PubMed, Scopus, and Web of Science were searched for relevant studies published before September 2017. We examined the study designs, the metabolomics approaches, and the reporting methodological quality following PRISMA statement. RESULTS AND CONCLUSION: The included 25 studies primarily focused on the identification rather than the validation of predictive capacity of potential biomarkers. The sample size ranged from 10 to 8760. External validation of the biomarker panels was observed in nine studies. The diagnostic area under the curve ranged from 0.68 to 1.00 (sensitivity: 0.43-1.00, specificity: 0.73-1.00). The effects of patients' bio-parameters on metabolome alterations in a context-dependent manner have not been thoroughly elucidated. The most reported candidates were glutamic acid and histidine in seven studies, and glutamine and isoleucine in five studies, leading to the predominant enrichment of amino acid-related pathways. Notably, 46 metabolites were estimated in at least two studies. Specific challenges and potential pitfalls to provide better insights into future research directions were thoroughly discussed. Our investigation suggests that metabolomics is a robust approach that will improve the diagnostic assessment of pancreatic cancer. Further studies are warranted to validate their validity in multi-clinical settings.
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Affiliation(s)
- Nguyen Phuoc Long
- Research Institute of Pharmaceutical Sciences and College of Pharmacy, Seoul National University, Seoul, 08826, South Korea
| | - Sang Jun Yoon
- Research Institute of Pharmaceutical Sciences and College of Pharmacy, Seoul National University, Seoul, 08826, South Korea
| | - Nguyen Hoang Anh
- Research Institute of Pharmaceutical Sciences and College of Pharmacy, Seoul National University, Seoul, 08826, South Korea
| | - Tran Diem Nghi
- School of Medicine, Vietnam National University, Ho Chi Minh City, 700000, Vietnam
| | - Dong Kyu Lim
- Research Institute of Pharmaceutical Sciences and College of Pharmacy, Seoul National University, Seoul, 08826, South Korea
| | - Yu Jin Hong
- Research Institute of Pharmaceutical Sciences and College of Pharmacy, Seoul National University, Seoul, 08826, South Korea
| | - Soon-Sun Hong
- Department of Drug Development, College of Medicine, Inha University, Incheon, 22212, South Korea
| | - Sung Won Kwon
- Research Institute of Pharmaceutical Sciences and College of Pharmacy, Seoul National University, Seoul, 08826, South Korea.
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35
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Ma WJ, Wu ZR, Shrestha A, Yang Q, Hu HJ, Wang JK, Liu F, Zhou RX, Li QS, Li FY. Effectiveness of additional resection of the invasive cancer-positive proximal bile duct margin in cases of hilar cholangiocarcinoma. Hepatobiliary Surg Nutr 2018; 7:251-269. [PMID: 30221153 DOI: 10.21037/hbsn.2018.03.14] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Background The survival benefits of additional resection of the positive proximal ductal margin (PM) in hilar cholangiocarcinoma (HCCA) remains controversial. This retrospective study investigated the effectiveness of additional resection of the invasive cancer PM under different levels of preoperative carbohydrate antigen 19-9 (CA19-9). Methods Patients who underwent hepatectomy for HCCA from 2000 to 2017 were analyzed. Surgical variables, resection margin status, length of the PM (LPM), prognostic factors, and survival were evaluated. Results A total of 228 patients were enrolled: 175 PM(-) without additional resection patients (group A), 21 PM(-) after additional resection (group B), 16 PM(+) without additional resection (group C), and 16 PM(+) after additional resection (group D). The median survival of group B (20.99 months) was similar to that of group A (23.00 months; P=0.16), and both were significantly better than those of group C (11.60 months) and D (9.50 months), especially when preoperative CA19-9>150 U/mL (P<0.05). The survival of patients with an LPM >10 mm was significantly better compared with those with an LPM ≤10 mm, especially when preoperative CA19-9 was >150 U/mL (P<0.05). Only in the LPM >10 mm group, the survival of group B was comparable with that of group A (P>0.05). Conclusions HCCA patients could get a survival benefit from a negative PM resulting from additional resection. Survival could be comparable with that of negative PM without additional resection among HCCA patients. An LPM >10 mm is possibly more associated with better survival compared with whether additional resection of the positive PM is performed under different levels of preoperative CA19-9.
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Affiliation(s)
- Wen-Jie Ma
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Zhen-Ru Wu
- Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Anuj Shrestha
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.,Department of General Surgery, Andaki Medical College, Pokhara, Nepal
| | - Qin Yang
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Hai-Jie Hu
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Jun-Ke Wang
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Fei Liu
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Rong-Xing Zhou
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Quan-Sheng Li
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Fu-Yu Li
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
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ENO1 Overexpression in Pancreatic Cancer Patients and Its Clinical and Diagnostic Significance. Gastroenterol Res Pract 2018; 2018:3842198. [PMID: 29483925 PMCID: PMC5816842 DOI: 10.1155/2018/3842198] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2017] [Revised: 12/16/2017] [Accepted: 01/03/2018] [Indexed: 12/18/2022] Open
Abstract
We investigated in this study the expression of ENO1 in tissues and plasma of PDAC patients to evaluate its clinicopathological and diagnostic significance. ENO1 protein expression was detected in tissue microarray of human PDAC and adjacent noncancer tissues. Electrochemiluminescence immunoassay and amplified luminescent proximity homogeneous assay (AlphaLISA) were performed to measure CA19-9 and ENO1 concentration in plasma from PDAC patients and healthy controls. We demonstrated that ENO1 overexpression is positively correlated with clinical stage, lymph node metastasis, and poor prognosis of PDAC; ENO1 may function as a hopeful candidate diagnostic marker in combination with CA19-9 in PDAC diagnosis.
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Lin C, Zhao GC, Xu YD, Wang DS, Jin DY, Ji Y, Lou WH, Wu WC. Increased expression of αTubulin is associated with poor prognosis in patients with pancreatic cancer after surgical resection. Oncotarget 2018; 7:60657-60664. [PMID: 27447976 PMCID: PMC5312409 DOI: 10.18632/oncotarget.10630] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2016] [Accepted: 06/07/2016] [Indexed: 12/17/2022] Open
Abstract
Background αTubulin, the essential orchestrator of cytoskeletal protein polymers, critical for cell growth and division, motility, signaling development and maintenance of cell shape, plays vital roles in the oncogenesis and progression of various types of cancer, but its role in prognosis of pancreatic cancer patients remains unknown. The aim of this study was to investigate its prognostic value in patients with pancreatic cancer after surgical resection. Results αTubulin expression in pancreatic cancer was significantly associated with N classification (p = 0.013) and TNM stage (p = 0.025). Increased expression of αTubulin in tumoral tissue was associated with decreased overall survival rate (p = 0.002). Multivariate Cox regression analysis suggested that αTubulin expression was an independent prognostic indicator for pancreatic cancer except for T and N classification (p = 0.002). Using multivariate analysis, αTubulin expression, CA19-9, and N classification were selected to generate the nomogram to predict the 1-year and 3-year overall survival. The c-index of this model was 0.692. The calibration curve for probability of survival showed good agreement between prediction by nomogram and actual observation. Methods αTubulin expression was evaluated by tissue microarrays from 124 pancreatic cancer patients and statistically assessed for correlations with the clinical profiles and the prognosis of the patients with pancreatic cancer. The prognostic nomogram was designed to predict 1-year and 3-year overall survival probability. Conclusions αTubulin expression might be an independent prognostic factor for pancreatic cancer after surgical resection and could potentially be a high-priority therapeutic target. Incorporating αTubulin expression into CA19-9 and N classification can provide a good prognostic model.
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Affiliation(s)
- Chao Lin
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Guo-Chao Zhao
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ya-Dong Xu
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Dan-Song Wang
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Da-Yong Jin
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yuan Ji
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wen-Hui Lou
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wen-Chuan Wu
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
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Goh SK, Gold G, Christophi C, Muralidharan V. Serum carbohydrate antigen 19-9 in pancreatic adenocarcinoma: a mini review for surgeons. ANZ J Surg 2017; 87:987-992. [PMID: 28803454 DOI: 10.1111/ans.14131] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Accepted: 05/24/2017] [Indexed: 12/12/2022]
Abstract
The optimal management of oncological conditions is reflected by the careful interpretation of investigations for screening, diagnosis, staging, prognostication and surveillance. Serum tumour markers are examples of commonly requested tests in conjunction with other imaging and endoscopic tests that are used to help clinicians to stratify therapeutic decisions. Serum carbohydrate antigen 19-9 (CA19-9) is a key biomarker for pancreatic cancers. Although this biomarker is considered clinically useful and informative, clinicians are often challenged by the accurate interpretation of elevated serum CA19-9 levels. Recognizing the pitfalls of normal and abnormal serum CA19-9 concentrations will facilitate its appropriate use. In this review, we appraised the biomarker, serum CA19-9, and highlighted the clinical utility and limitations of serum CA19-9 in the investigation and management of pancreatic cancers.
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Affiliation(s)
- Su Kah Goh
- Hepato-Pancreato-Biliary and Transplant Unit, Austin Hospital, Melbourne, Victoria, Australia
- Department of Surgery, The University of Melbourne, Melbourne, Victoria, Australia
| | - Grace Gold
- Hepato-Pancreato-Biliary and Transplant Unit, Austin Hospital, Melbourne, Victoria, Australia
- Department of Surgery, The University of Melbourne, Melbourne, Victoria, Australia
| | - Christopher Christophi
- Hepato-Pancreato-Biliary and Transplant Unit, Austin Hospital, Melbourne, Victoria, Australia
- Department of Surgery, The University of Melbourne, Melbourne, Victoria, Australia
| | - Vijayaragavan Muralidharan
- Hepato-Pancreato-Biliary and Transplant Unit, Austin Hospital, Melbourne, Victoria, Australia
- Department of Surgery, The University of Melbourne, Melbourne, Victoria, Australia
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Ko J, Bhagwat N, Yee SS, Ortiz N, Sahmoud A, Black T, Aiello NM, McKenzie L, O'Hara M, Redlinger C, Romeo J, Carpenter EL, Stanger BZ, Issadore D. Combining Machine Learning and Nanofluidic Technology To Diagnose Pancreatic Cancer Using Exosomes. ACS NANO 2017; 11:11182-11193. [PMID: 29019651 DOI: 10.1021/acsnano.7b05503] [Citation(s) in RCA: 158] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/03/2023]
Abstract
Circulating exosomes contain a wealth of proteomic and genetic information, presenting an enormous opportunity in cancer diagnostics. While microfluidic approaches have been used to successfully isolate cells from complex samples, scaling these approaches for exosome isolation has been limited by the low throughput and susceptibility to clogging of nanofluidics. Moreover, the analysis of exosomal biomarkers is confounded by substantial heterogeneity between patients and within a tumor itself. To address these challenges, we developed a multichannel nanofluidic system to analyze crude clinical samples. Using this platform, we isolated exosomes from healthy and diseased murine and clinical cohorts, profiled the RNA cargo inside of these exosomes, and applied a machine learning algorithm to generate predictive panels that could identify samples derived from heterogeneous cancer-bearing individuals. Using this approach, we classified cancer and precancer mice from healthy controls, as well as pancreatic cancer patients from healthy controls, in blinded studies.
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Affiliation(s)
- Jina Ko
- Department of Bioengineering and ∥Department of Electrical and Systems Engineering, School of Engineering and Applied Sciences, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States
- Division of Gastroenterology and §Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine and ⊥Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States
| | - Neha Bhagwat
- Department of Bioengineering and ∥Department of Electrical and Systems Engineering, School of Engineering and Applied Sciences, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States
- Division of Gastroenterology and §Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine and ⊥Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States
| | - Stephanie S Yee
- Department of Bioengineering and ∥Department of Electrical and Systems Engineering, School of Engineering and Applied Sciences, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States
- Division of Gastroenterology and §Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine and ⊥Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States
| | - Natalia Ortiz
- Department of Bioengineering and ∥Department of Electrical and Systems Engineering, School of Engineering and Applied Sciences, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States
- Division of Gastroenterology and §Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine and ⊥Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States
| | - Amine Sahmoud
- Department of Bioengineering and ∥Department of Electrical and Systems Engineering, School of Engineering and Applied Sciences, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States
- Division of Gastroenterology and §Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine and ⊥Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States
| | - Taylor Black
- Department of Bioengineering and ∥Department of Electrical and Systems Engineering, School of Engineering and Applied Sciences, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States
- Division of Gastroenterology and §Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine and ⊥Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States
| | - Nicole M Aiello
- Department of Bioengineering and ∥Department of Electrical and Systems Engineering, School of Engineering and Applied Sciences, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States
- Division of Gastroenterology and §Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine and ⊥Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States
| | - Lydie McKenzie
- Department of Bioengineering and ∥Department of Electrical and Systems Engineering, School of Engineering and Applied Sciences, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States
- Division of Gastroenterology and §Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine and ⊥Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States
| | - Mark O'Hara
- Department of Bioengineering and ∥Department of Electrical and Systems Engineering, School of Engineering and Applied Sciences, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States
- Division of Gastroenterology and §Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine and ⊥Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States
| | - Colleen Redlinger
- Department of Bioengineering and ∥Department of Electrical and Systems Engineering, School of Engineering and Applied Sciences, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States
- Division of Gastroenterology and §Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine and ⊥Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States
| | - Janae Romeo
- Department of Bioengineering and ∥Department of Electrical and Systems Engineering, School of Engineering and Applied Sciences, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States
- Division of Gastroenterology and §Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine and ⊥Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States
| | - Erica L Carpenter
- Department of Bioengineering and ∥Department of Electrical and Systems Engineering, School of Engineering and Applied Sciences, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States
- Division of Gastroenterology and §Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine and ⊥Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States
| | - Ben Z Stanger
- Department of Bioengineering and ∥Department of Electrical and Systems Engineering, School of Engineering and Applied Sciences, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States
- Division of Gastroenterology and §Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine and ⊥Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States
| | - David Issadore
- Department of Bioengineering and ∥Department of Electrical and Systems Engineering, School of Engineering and Applied Sciences, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States
- Division of Gastroenterology and §Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine and ⊥Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States
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Papafragkakis C, Lee J. Comprehensive management of cholangiocarcinoma: Part I. Diagnosis. INTERNATIONAL JOURNAL OF GASTROINTESTINAL INTERVENTION 2017. [DOI: 10.18528/gii1500341] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Affiliation(s)
- Charilaos Papafragkakis
- epartment of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jeffrey Lee
- epartment of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Detection of Circulating Tumor Cells Using Negative Enrichment Immunofluorescence and an In Situ Hybridization System in Pancreatic Cancer. Int J Mol Sci 2017; 18:ijms18040622. [PMID: 28333072 PMCID: PMC5412265 DOI: 10.3390/ijms18040622] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2017] [Revised: 03/05/2017] [Accepted: 03/07/2017] [Indexed: 12/12/2022] Open
Abstract
Pancreatic cancer (PC) is the most lethal type of gastrointestinal cancer, and early detection and monitoring is an urgent problem. Circulating tumor cells (CTCs) are emerging as a non-invasive biomarker for tumor detection. However, the low sensitivity is a main problem in the traditional CellSearch System for detecting CTCs, especially in patients with PC. In this study, we used negative enrichment (NE), immunofluorescence and in situ hybridization (FISH) of chromosome 8 (NE-iFISH) to capture and identify CTCs in PC patients. We showed that the NE-iFISH system exhibited a dramatically high detection rate of CTCs in PC patients (90%). The diagnostic rate of PC reached 97.5% when combining CTCs ≥ 2 and carbohydrate antigen 19-9 (CA19-9) > 37 µmol/L. The 1-year survival in the group of CTCs < 3 was significantly higher than that of CTCs ≥ 3 (p = 0.043). In addition, we analyzed the role of chromosomal instability in CTCs detection. The group of triploid (three hybridization signals of chromosome 8) CTCs ≥ 3 showed a shorter 1-year survival (p = 0.0279) and overall survival (p = 0.0188) than the group with triploid CTCs < 3. Importantly, the triploid CTC number but not the overall CTC counts could be a predictor of chemo-sensitivity. Moreover, circulating tumor microembolus (CTMs) were found in stage IV patients, and were positively related to the poor response to chemotherapy. In conclusion, the NE-iFISH system significantly improved the positive detection rate of CTCs and triploid CTC could be used to predict prognosis or the response to the chemotherapy of PC patients. CTM is a potential indicator of the chemotherapeutic effect in advanced PC patients.
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Rahnemai-Azar AA, Weisbrod A, Dillhoff M, Schmidt C, Pawlik TM. Intrahepatic cholangiocarcinoma: Molecular markers for diagnosis and prognosis. Surg Oncol 2017; 26:125-137. [PMID: 28577718 DOI: 10.1016/j.suronc.2016.12.009] [Citation(s) in RCA: 68] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2016] [Revised: 12/24/2016] [Accepted: 12/29/2016] [Indexed: 02/08/2023]
Abstract
Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver tumor with increasing incidence worldwide. The outcome of patients with iCCA is dismal owing to tumor's aggressiveness, late diagnosis and lack of effective treatment options. Detection of the tumor at early stages may make surgical resection, as only potential curative treatment, more feasible. Unfortunately, despite recent developments in imaging modalities and laboratory tests, the diagnosis of iCCA remains challenging and patients often present in advanced stages when surgery cannot be offered. Moreover, accurate assessment of disease burden is critical to optimize management strategy, including the use of adjuvant therapies and clinical trials. Identifying iCCA specific diagnostic and prognostic biomarkers has been a focus of interest among many investigators with a progressive increase in data on iCCA related to advances in "omics" technologies. We herein summarize iCCA biomarkers and define the molecular mechanisms underlying iCCA carcinogenesis, as well as highlight potential diagnostic and prognostic application of molecular biomarkers.
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Affiliation(s)
- Amir A Rahnemai-Azar
- Department of Surgery, University of Washington Medical Center, Seattle, WA, USA
| | - Allison Weisbrod
- Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH, USA
| | - Mary Dillhoff
- Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH, USA
| | - Carl Schmidt
- Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH, USA
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH, USA.
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Zhao YP, Zhou PT, Ji WP, Wang H, Fang M, Wang MM, Yin YP, Jin G, Gao CF. Validation of N-glycan markers that improve the performance of CA19-9 in pancreatic cancer. Clin Exp Med 2017; 17:9-18. [PMID: 26714469 DOI: 10.1007/s10238-015-0401-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2015] [Accepted: 11/02/2015] [Indexed: 01/05/2023]
Abstract
Pancreatic cancer (PC) has a high mortality rate because it is usually diagnosed late. Glycosylation of proteins is known to change in tumor cells during the development of PC. The objectives of this study were to identify and validate the diagnostic value of novel biomarkers based on N-glycomic profiling for PC. In total, 217 individuals including subjects with PC, pancreatitis, and healthy controls were divided randomly into a training group (n = 164) and validation groups (n = 53). Serum N-glycomic profiling was analyzed by DSA-FACE. The diagnostic model was constructed based on N-glycan markers with logistic stepwise regression. The diagnostic performance of the model was assessed further in validation cohort. The level of total core fucose residues was increased significantly in PC. Two diagnostic models designated GlycoPCtest and PCmodel (combining GlycoPCtest and CA19-9) were constructed to differentiate PC from normal. The area under the receiver operating characteristic curve (AUC) of PCmodel was higher than that of CA19-9 (0.925 vs. 0.878). The diagnostic models based on N-glycans are new, valuable, noninvasive alternatives for identifying PC. The diagnostic efficacy is improved by combined GlycoPCtest and CA19-9 for the discrimination of patients with PC from healthy controls.
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Affiliation(s)
- Yun-Peng Zhao
- Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Rd, Shanghai, 200438, China
| | - Ping-Ting Zhou
- Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Rd, Shanghai, 200438, China
| | - Wei-Ping Ji
- Department of Surgery, Changhai Hospital, Second Military Medical University, 116 Changhai Rd, Shanghai, 200438, China
| | - Hao Wang
- Department of Laboratory Medicine, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Meng Fang
- Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Rd, Shanghai, 200438, China
| | - Meng-Meng Wang
- Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Rd, Shanghai, 200438, China
| | - Yue-Peng Yin
- Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Rd, Shanghai, 200438, China
| | - Gang Jin
- Department of Surgery, Changhai Hospital, Second Military Medical University, 116 Changhai Rd, Shanghai, 200438, China.
| | - Chun-Fang Gao
- Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Rd, Shanghai, 200438, China.
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Gu X, Liu R. Application of 18F-FDG PET/CT combined with carbohydrate antigen 19-9 for differentiating pancreatic carcinoma from chronic mass-forming pancreatitis in Chinese elderly. Clin Interv Aging 2016; 11:1365-1370. [PMID: 27729779 PMCID: PMC5047721 DOI: 10.2147/cia.s115254] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVE The current study was designed to analyze the value of 18F-FDG positron emission tomography/computed tomography (PET/CT) combined with carbohydrate antigen 19-9 (CA19-9) in differentiating pancreatic carcinoma (PC) from chronic mass-forming pancreatitis (CMFP) in Chinese elderly. METHODS As it is impossible to differentially diagnose PC from CMFP, 60 participants older than 65 years with focal pancreatic lesions were scanned by 18F-FDG PET/CT and their CA19-9 levels were tested. Diagnoses of all participants were confirmed by comprehensive methods including aspiration biopsy, surgical pathology, and clinical follow-up of 12 months. Twenty participants with CMFP were included in CMFP group and 40 participants with PC in PC group. RESULTS In CMFP and PC groups, 46 participants showed increased 18F-FDG uptake, 43 had elevated CA19-9 levels, and 38 participants had both increased 18F-FDG uptake and elevated CA19-9 levels. Standardized uptake value maximum of PC group (5.98±2.27) was significantly different from CMFP group (2.58±1.81, P<0.05). Sensitivity, specificity, and accuracy of 18F-FDG PET/CT in differentiating PC from CMFP were 95%, 60%, and 83.3%, respectively. CA19-9 levels of PC group (917.44±1,088.24) were significantly different from CMFP group (19.09±19.54, P<0.05). Sensitivity, specificity, and accuracy of CA19-9 levels in differentiating PC from CMFP were 87.5%, 60%, and 78.3%, respectively. Sensitivity, specificity, and accuracy of 18F-FDG PET/CT combined with CA19-9 levels in differentiating PC from CMFP were 90%, 90%, and 90%, respectively. CONCLUSION 18F-FDG PET/CT had reliable sensitivity, specificity, and accuracy in differentiating PC from CMFP, and CA19-9 levels could be helpful in 18F-FDG PET/CT for differentiating PC from CMFP in Chinese elderly. Moreover, 18F-FDG PET/CT combined with CA19-9 levels was found to be an effective method to differentially diagnose PC from CMFP and has paved the way for the timely and safe treatment of PC and CMFP in Chinese elderly.
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Affiliation(s)
- Xinjin Gu
- Department of Hepatobiliary Surgery, Chinese People’s Liberation Army General Hospital and Hainan Branch, Sanya
| | - Rong Liu
- Department of Hepatobiliary and Pancreatic Surgical Oncology, Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of China
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Lin C, Wu WC, Zhao GC, Wang DS, Lou WH, Jin DY. ITRAQ-based quantitative proteomics reveals apolipoprotein A-I and transferrin as potential serum markers in CA19-9 negative pancreatic ductal adenocarcinoma. Medicine (Baltimore) 2016; 95:e4527. [PMID: 27495108 PMCID: PMC4979862 DOI: 10.1097/md.0000000000004527] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Currently the diagnosis of pancreatic ductal adenocarcinoma (PDAC) relies on CA19-9 and radiological means, whereas some patients do not have elevated levels of CA19-9 secondary to pancreatic cancer. The purpose of this study was to identify potential serum biomarkers for CA19-9 negative PDAC.A total of 114 serum samples were collected from 3 groups: CA19-9 negative PDAC patients (n = 34), CA19-9 positive PDAC patients (n = 44), and healthy volunteers (n = 36), whereas the first 12 samples from each group were used for isobaric tags for relative and absolute quantitation (iTRAQ) analysis. Thereafter, candidate biomarkers were selected for validation by enzyme-linked immunosorbent assay (ELISA) with the rest specimens.Using the iTRAQ approach, a total of 5 proteins were identified as significantly different between CA19-9 negative PDAC patients and healthy subjects according to our defined criteria. Apolipoprotein A-I (APOA-I) and transferrin (TF) were selected to validate the proteomic results by ELISA in a further 78 serum specimens. It revealed that TF significantly correlated with the degree of histological differentiation (P = 0.042), and univariate and multivariate analyses indicated that TF is an independent prognostic factor for survival (hazard ratio, 0.302; 95% confidence interval, 0.118-0.774; P = 0.013) of patients with PDAC after curative surgery.ITRAQ-based quantitative proteomics revealed that APOA-I and TF may be potential CA19-9 negative PDAC serum markers.
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Affiliation(s)
| | - Wen-Chuan Wu
- Department of General Surgery, Zhongshan Hospital Fudan University, Shanghai, China
- Correspondence: Wen-Chuan Wu, Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China (e-mail: )
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Chen Y, Cha Z, Fang W, Qian B, Yu W, Li W, Yu G, Gao Y. The prognostic potential and oncogenic effects of PRR11 expression in hilar cholangiocarcinoma. Oncotarget 2016; 6:20419-33. [PMID: 25971332 PMCID: PMC4653015 DOI: 10.18632/oncotarget.3983] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2014] [Accepted: 04/10/2015] [Indexed: 12/15/2022] Open
Abstract
PRR11 is a newly identified oncogene in lung cancer, yet its role in others tumors remains unclear. Gastrointestinal tissue microarrays were used to evaluate PRR11 expression and its association with clinical outcome was analyzed in patients with hilar cholangiocarcinoma. Overexpression of PRR11 was observed in esophageal, gastric, pancreatic, colorectal, and hilar cholangiocarcinoma. Expression of PRR11 correlated with lymph node metastasis and CA199 level in two HC patient cohorts. After an R0 resection, a high level of PRR11 expression was found to be an independent indicator of recurrence (P = 0.001). In cell culture, PRR11 silencing resulted in decreased cellular proliferation, cell migration, tumor growth of QBC939 cells. Microarray analysis revealed that several genes involved in cell proliferation, cell adhesion, and cell migration were altered in PRR11-knockout cells, including: vimentin (VIM), Ubiquitin carboxyl-terminal hydrolase 1 (UCHL1), early growth response protein (EGR1), and System A amino acid transporter1 (SNAT1). Silencing PRR11 inhibited the expression of UCHL1, EGR1, and SNAT1 proteins, with immunoassays revealing a significant correlation among the levels of these four proteins. These results indicate that PRR11 is an independent prognostic indicator for patients with HC.
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Affiliation(s)
- Ying Chen
- Department of Pathology, Changhai Hospital, Shanghai, China
| | - Zhanshan Cha
- Department of Transfusion, Changhai Hospital, Shanghai, China
| | - Wenzheng Fang
- Department of Oncology, Fuzhou General Hospital, Fuzhou, Fujian Province, China
| | - Baohua Qian
- Department of Transfusion, Changhai Hospital, Shanghai, China
| | - Wenlong Yu
- Department of Surgery, Eastern Hepatobiliary Hospital, Shanghai, China
| | - Wenfeng Li
- Department of Radiation Oncology, First Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang, China
| | - Guanzhen Yu
- Department of Medical Oncology, Changzheng Hospital, Shanghai, China.,Department of Oncology, East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yong Gao
- Department of Oncology, East Hospital, Tongji University School of Medicine, Shanghai, China
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47
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Guo X, Lv X, Fang C, Lv X, Wang F, Wang D, Zhao J, Ma Y, Xue Y, Bai Q, Yao X, Chen Y. Dysbindin as a novel biomarker for pancreatic ductal adenocarcinoma identified by proteomic profiling. Int J Cancer 2016; 139:1821-9. [PMID: 27281120 DOI: 10.1002/ijc.30227] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2014] [Revised: 04/27/2016] [Accepted: 05/30/2016] [Indexed: 12/20/2022]
Abstract
Pancreatic adenocarcinoma (PDAC) is known to have a poor prognosis partly because of lack of effective biomarkers. In the test set, we investigated dysbindin (DTNBP1) as a potential biomarker for PDAC by comparing preoperative and postoperative serum mass spectrometry (MS) proteomic profilings. Of the included 50 PDAC patients, 42 (positivity of 84.0%) detected a lower MS peak in postoperative serums than preoperative ones which was then identified as dysbindin. In the verification set, receiver operating characteristics (ROC) were used to assess diagnostic efficiency. 550 participants were included in the verification set [250 with PDAC, 80 with benign biliary obstruction (BBO), 70 with chronic pancreatitis (CP) and 150 healthy donors (HD)]. Dysbindin was increased in PDAC patient sera than in all controls. ROC curves revealed the optimum diagnostic cutoff for dysbindin was 699.16 pg/ml [area under curve (AUC) 0.849 (95% CI 0.812-0.885), sensitivity 81.9% and specificity 84.7%]. Raised concentration of dysbindin in sera could differentiate PDAC from BBO, CP and HD. Moreover, dysbindin maintained its diagnostic accuracy for PDAC patients who were CA19-9 negative [AUC 0.875 (95% CI 0.804-0.945), sensitivity 83.0%, specificity 89.0%] and for patients with benign biliary obstruction [AUC 0.849 (95% CI 0.803-0.894), sensitivity 82.3%, specificity 84.0%].Our discovery of dysbindin may complement measurement of CA19-9 in the diagnosis of PDAC and help to discriminate PDAC from other pancreatic diseases or begin biliary obstruction.
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Affiliation(s)
- Xin Guo
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.,Department of Endoscopic Surgery, the people's Liberation Army 451st hospital, Xi'an, Shaanxi, People's Republic of China
| | - Xiaohui Lv
- Department of Endoscopic Surgery, the people's Liberation Army 451st hospital, Xi'an, Shaanxi, People's Republic of China
| | - Cheng Fang
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China
| | - Xing Lv
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China
| | - Fengsong Wang
- Department ofgynecology and obstetrics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.,Department of Biology, School of Life Science, Anhui Medical University, Hefei, Anhui, People's Republic of China
| | - Dongmei Wang
- Department of Hefei Laboratory for Physical Sciences at Microscale, School of Life Science, University of Science and Technology of China, Hefei, Anhui, People's Republic of China
| | - Jun Zhao
- Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China
| | - Yueyun Ma
- Department of Clinical Laboratory Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China
| | - Yu Xue
- Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China
| | - Quan Bai
- Institute of Modern Separation Science, College of Chemistry & Materials Science, Northwest University, Xi'an, Shaanxi, People's Republic of China
| | - Xuebiao Yao
- Department of Hefei Laboratory for Physical Sciences at Microscale, School of Life Science, University of Science and Technology of China, Hefei, Anhui, People's Republic of China
| | - Yong Chen
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China
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48
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Wen S, Li Z, Feng J, Bai J, Lin X, Huang H. Metabonomic changes from pancreatic intraepithelial neoplasia to pancreatic ductal adenocarcinoma in tissues from rats. Cancer Sci 2016; 107:836-45. [PMID: 27019331 PMCID: PMC4968602 DOI: 10.1111/cas.12939] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2016] [Revised: 03/24/2016] [Accepted: 03/25/2016] [Indexed: 01/12/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors and is difficult to diagnose in the early phase. This study was aimed at obtaining the metabolic profiles and characteristic metabolites of pancreatic intraepithelial neoplasia (PanIN) and PDAC tissues from Sprague-Dawley (SD) rats to establish metabonomic methods used in the early diagnosis of PDAC. In the present study, the animal models were established by embedding 7,12-dimethylbenzanthracene (DMBA) in the pancreas of SD rats to obtain PanIN and PDAC tissues. After the preprocessing of tissues, (1) H nuclear magnetic resonance (NMR) spectroscopy combined with multivariate and univariate statistical analysis was applied to identify the potential metabolic signatures and the corresponding metabolic pathways. Pattern recognition models were successfully established and differential metabolites, including glucose, amino acids, carboxylic acids and coenzymes, were screened out. Compared with the control, the trends in the variation of several metabolites were similar in both PanIN and PDAC. Kynurenate and methionine levels were elevated in PanIN but decreased in PDAC, thus, could served as biomarkers to distinguish PanIN from PDAC. Our results suggest that NMR-based techniques combined with multivariate statistical analysis can distinguish the metabolic differences among PanIN, PDAC and normal tissues, and, therefore, present a promising approach for physiopathologic metabolism investigations and early diagnoses of PDAC.
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Affiliation(s)
- Shi Wen
- Department of General SurgeryFujian Medical University Union HospitalFuzhouChina
| | - Zhishui Li
- Department of Electronic ScienceFujian Provincial Key Laboratory of Plasma and Magnetic ResonanceXiamen UniversityXiamenChina
| | - Jianghua Feng
- Department of Electronic ScienceFujian Provincial Key Laboratory of Plasma and Magnetic ResonanceXiamen UniversityXiamenChina
| | - Jianxi Bai
- Department of General SurgeryFujian Medical University Union HospitalFuzhouChina
| | - Xianchao Lin
- Department of General SurgeryFujian Medical University Union HospitalFuzhouChina
| | - Heguang Huang
- Department of General SurgeryFujian Medical University Union HospitalFuzhouChina
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49
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Bhasin MK, Ndebele K, Bucur O, Yee EU, Otu HH, Plati J, Bullock A, Gu X, Castan E, Zhang P, Najarian R, Muraru MS, Miksad R, Khosravi-Far R, Libermann TA. Meta-analysis of transcriptome data identifies a novel 5-gene pancreatic adenocarcinoma classifier. Oncotarget 2016; 7:23263-81. [PMID: 26993610 PMCID: PMC5029625 DOI: 10.18632/oncotarget.8139] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2016] [Accepted: 02/28/2016] [Indexed: 12/12/2022] Open
Abstract
PURPOSE Pancreatic ductal adenocarcinoma (PDAC) is largely incurable due to late diagnosis. Superior early detection biomarkers are critical to improving PDAC survival and risk stratification. EXPERIMENTAL DESIGN Optimized meta-analysis of PDAC transcriptome datasets identified and validated key PDAC biomarkers. PDAC-specific expression of a 5-gene biomarker panel was measured by qRT-PCR in microdissected patient-derived FFPE tissues. Cell-based assays assessed impact of two of these biomarkers, TMPRSS4 and ECT2, on PDAC cells. RESULTS A 5-gene PDAC classifier (TMPRSS4, AHNAK2, POSTN, ECT2, SERPINB5) achieved on average 95% sensitivity and 89% specificity in discriminating PDAC from non-tumor samples in four training sets and similar performance (sensitivity = 94%, specificity = 89.6%) in five independent validation datasets. This classifier accurately discriminated PDAC from chronic pancreatitis (AUC = 0.83), other cancers (AUC = 0.89), and non-tumor from PDAC precursors (AUC = 0.92) in three independent datasets. Importantly, the classifier distinguished PanIN from healthy pancreas in the PDX1-Cre;LSL-KrasG12D PDAC mouse model. Discriminatory expression of the PDAC classifier genes was confirmed in microdissected FFPE samples of PDAC and matched surrounding non-tumor pancreas or pancreatitis. Notably, knock-down of TMPRSS4 and ECT2 reduced PDAC soft agar growth and cell viability and TMPRSS4 knockdown also blocked PDAC migration and invasion. CONCLUSIONS This study identified and validated a highly accurate 5-gene PDAC classifier for discriminating PDAC and early precursor lesions from non-malignant tissue that may facilitate early diagnosis and risk stratification upon validation in prospective clinical trials. Cell-based experiments of two overexpressed proteins encoded by the panel, TMPRSS4 and ECT2, suggest a causal link to PDAC development and progression, confirming them as potential therapeutic targets.
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Affiliation(s)
- Manoj K. Bhasin
- Department of Medicine, BIDMC Genomics, Proteomics, Bioinformatics and Systems Biology Center, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Kenneth Ndebele
- Department of Pathology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Octavian Bucur
- Department of Pathology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA
- Department of Molecular Cell Biology, Institute of Biochemistry of the Romanian Academy, Bucharest, Romania
| | - Eric U. Yee
- Department of Pathology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Hasan H. Otu
- Department of Electrical and Computer Engineering, University of Nebraska-Lincoln, Lincoln, Nebraska, USA
| | - Jessica Plati
- Department of Pathology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Andrea Bullock
- Division of Hematology and Oncology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Xuesong Gu
- Department of Medicine, BIDMC Genomics, Proteomics, Bioinformatics and Systems Biology Center, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Eduardo Castan
- Department of Medicine, BIDMC Genomics, Proteomics, Bioinformatics and Systems Biology Center, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Peng Zhang
- Department of Medicine, BIDMC Genomics, Proteomics, Bioinformatics and Systems Biology Center, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Robert Najarian
- Department of Pathology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Maria S. Muraru
- Department of Pathology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Rebecca Miksad
- Division of Hematology and Oncology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Roya Khosravi-Far
- Department of Pathology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Towia A. Libermann
- Department of Medicine, BIDMC Genomics, Proteomics, Bioinformatics and Systems Biology Center, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA
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50
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Seldon CS, Colbert LE, Hall WA, Fisher SB, Yu DS, Landry JC. Chromodomain-helicase-DNA binding protein 5, 7 and pronecrotic mixed lineage kinase domain-like protein serve as potential prognostic biomarkers in patients with resected pancreatic adenocarcinomas. World J Gastrointest Oncol 2016; 8:358-365. [PMID: 27096031 PMCID: PMC4824714 DOI: 10.4251/wjgo.v8.i4.358] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2015] [Revised: 12/05/2015] [Accepted: 01/11/2016] [Indexed: 02/05/2023] Open
Abstract
Pancreatic cancer is one of the deadliest cancers with a very poor prognosis. Recently, there has been a significant increase in research directed towards identifying potential biomarkers that can be used to diagnose and provide prognostic information for pancreatic cancer. These markers can be used clinically to optimize and personalize therapy for individual patients. In this review, we focused on 3 biomarkers involved in the DNA damage response pathway and the necroptosis pathway: Chromodomain-helicase-DNA binding protein 5, chromodomain-helicase-DNA binding protein 7, and mixed lineage kinase domain-like protein. The aim of this article is to review present literature provided for these biomarkers and current studies in which their effectiveness as prognostic biomarkers are analyzed in order to determine their future use as biomarkers in clinical medicine. Based on the data presented, these biomarkers warrant further investigation, and should be validated in future studies.
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