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Razmi M, Tajik F, Hashemi F, Yazdanpanah A, Hashemi-Niasari F, Divsalar A. The Prognostic Importance of Ki-67 in Gastrointestinal Carcinomas: A Meta-analysis and Multi-omics Approach. J Gastrointest Cancer 2024; 55:599-624. [PMID: 38411875 DOI: 10.1007/s12029-024-01022-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/23/2024] [Indexed: 02/28/2024]
Abstract
PURPOSE This study aimed to determine if Ki-67, a commonly used marker to measure tumor proliferation, is a reliable prognostic factor in various types of gastrointestinal (GI) cancers based on current high-quality multivariable evidence. METHODS A comprehensive search was conducted in PubMed, Embase, Scopus, and ISI Web of Science databases to investigate the association between Ki-67 positivity and overall survival (OS) and disease/recurrence-free survival (DFS/RFS) in GI cancers. Heterogeneity was assessed using Chi-square-based Q and I2 analyses and publication bias using funnel plots and Egger's analysis. In addition, Ki-67 levels in different GI cancers were examined by different platforms. The prognostic capability of Ki-67, gene ontology (GO), and pathway enrichment analysis were obtained from GEPIA2 and STRING. RESULTS Totally, 61 studies, involving 13,034 patients, were deemed eligible for our evaluation. The combined hazard ratios (HRs) demonstrated the prediction ability of overexpressed Ki-67 for a worse OS (HR: 1.67, P < 0.001; HR: 1.37, P = 0.021) and DFS/RFS (HR: 2.06, P < 0.001) in hepatocellular and pancreatic malignancies, respectively, as confirmed by multi-omics databases. However, similar correlation was not found in esophageal, gastric, and colorectal cancers. Furthermore, most of the associations were identified to be robust based on different subcategories and publication bias assessment. Finally, enriched Ki-67-related genes were found to be involved in various important signaling pathways, such as cell cycle, P53 signaling network, and DNA damage responses. CONCLUSION This study supports that Ki-67 can serve as an independent prognostic biomarker for pancreatic and hepatocellular malignancies in clinical settings.
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Affiliation(s)
- Mahdieh Razmi
- Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran.
| | - Fatemeh Tajik
- Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Surgery, University of California, Irvine, CA, USA
| | - Farideh Hashemi
- Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Ayna Yazdanpanah
- Department of Tissue Engineering and Regenerative Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Hashemi-Niasari
- Department of Biochemistry, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
| | - Adeleh Divsalar
- Department of Cell and Molecular Sciences, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran
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Khamis T, Diab AAAA, Zahra MH, El-Dahmy SE, Abd Al-Hameed BA, Abdelkhalek A, Said MA, Abdellatif H, Fericean LM, Banatean-Dunea I, Arisha AH, Attia MS. The Antiproliferative Activity of Adiantum pedatum Extract and/or Piceatannol in Phenylhydrazine-Induced Colon Cancer in Male Albino Rats: The miR-145 Expression of the PI-3K/ Akt/ p53 and Oct4/ Sox2/ Nanog Pathways. Molecules 2023; 28:5543. [PMID: 37513415 PMCID: PMC10383735 DOI: 10.3390/molecules28145543] [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: 06/04/2023] [Revised: 07/13/2023] [Accepted: 07/18/2023] [Indexed: 07/30/2023] Open
Abstract
Colon cancer is one of the most common types of cancer worldwide, and its incidence is increasing. Despite advances in medical science, the treatment of colon cancer still poses a significant challenge. This study aimed to investigate the potential protective effects of Adiantum pedatum (AP) extract and/or piceatannol on colon cancer induced via phenylhydrazine (PHZ) in terms of the antioxidant and apoptotic pathways and histopathologic changes in the colons of male albino rats. The rats were randomly divided into eight groups: control, AP extract, piceatannol (P), PHZ, PHZ and AP treatments, PHZ and P treatments, PHZ and both AP and P, and PHZ and prophylaxis with both AP and P. The results demonstrated that PHZ induced oxidative damage, apoptosis, and histopathological changes compared to the control group. However, the administration of AP or P or AP + P as therapy or prophylaxis significantly ameliorated these changes and upregulated the colonic mir-145 and mRNA expression of P53 and PDCD-4 while downregulating the colonic mRNA expression of PI3K, AKT, c-Myc, CK-20, SOX-2, OCT-4, and NanoG compared to the PHZ group. These findings suggest that the candidate drugs may exert their anti-cancer effects through multiple mechanisms, including antioxidant and apoptotic activities.
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Affiliation(s)
- Tarek Khamis
- Department of Pharmacology and Laboratory of Biotechnology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt
| | | | - Mansour H Zahra
- Zoology Department, Faculty of Science, Zagazig University, Zagazig 44519, Egypt
| | - Samih Ebrahim El-Dahmy
- Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt
| | | | - Adel Abdelkhalek
- Faculty of Veterinary Medicine, Badr University in Cairo, Badr City 11829, Egypt
| | - Mahmoud A Said
- Zagazig University Hospital, Zagazig University, Zagazig 44511, Egypt
| | - Hussein Abdellatif
- Department of Human and Clinical Anatomy, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat 123, Oman
- Anatomy and Embryology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
| | - Liana Mihaela Fericean
- Department of Biology, Faculty of Agriculture, University of Life Sciences, King Mihai I" from Timisoara [ULST], Aradului St. 119, 300645 Timisoara, Romania
| | - Ioan Banatean-Dunea
- Department of Biology, Faculty of Agriculture, University of Life Sciences, King Mihai I" from Timisoara [ULST], Aradului St. 119, 300645 Timisoara, Romania
| | - Ahmed Hamed Arisha
- Department of Animal Physiology and Biochemistry, Faculty of Veterinary Medicine, Badr University in Cairo, Badr City 11829, Egypt
- Department of Physiology, Laboratory of Biotechnology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt
| | - Mai S Attia
- Zoology Department, Faculty of Science, Zagazig University, Zagazig 44519, Egypt
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Jo Y, Lee JH, Cho ES, Lee HS, Shin SJ, Park EJ, Baik SH, Lee KY, Kang J. Clinical Significance of Early Carcinoembryonic Antigen Change in Patients With Nonmetastatic Colorectal Cancer. Front Oncol 2022; 12:739614. [PMID: 35615159 PMCID: PMC9124957 DOI: 10.3389/fonc.2022.739614] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Accepted: 04/15/2022] [Indexed: 12/28/2022] Open
Abstract
Background This study aimed to evaluate the prognostic significance of preoperative, postoperative, and trajectory changes in carcinoembryonic antigen (CEA) levels in patients with colorectal cancer (CRC). Methods This retrospective study included patients who underwent surgical resection for nonmetastatic CRC. The optimal cutoff values of preoperative CEA (CEA-pre), early postoperative CEA (CEA-post), and CEA level change (CEA-delta) were determined to maximize the differences in overall survival (OS) among groups. The patients were divided into three groups according to CEA-trend: normal, low CEA-pre; normalized, high CEA-pre/low CEA-post; elevated, high CEA-pre/high CEA-post. The integrated area under the curve (iAUC) was used to compare the discriminatory power of all variables. Results A total of 1019 patients diagnosed with stage I–III CRC were enrolled. The optimal cutoff values of CEA level were determined as 2.3 ng/mL for CEA-pre, 2.3 ng/mL for CEA-post, and -0.93 ng/mL for CEA-delta. Although subgroup dichotomization showed that CEA-pre, CEA-post, CEA-delta, and CEA-trend were all associated with OS in univariate analysis, CEA-trend was the only independent prognostic factor in multivariate analysis. The iAUC of CEA-trend was superior to that of CEA-pre, CEA-post, and CEA-delta. Compared with the normal group, the normalized group showed worse OS (p=.0007) in stage II patients but similar OS (p=.067) in stage III patients. Conclusion The optimal cutoff value of CEA level in the preoperative and postoperative periods was determined to be 2.3 ng/mL, and the combination of CEA-pre and CEA-post showed better prognostic stratification. However, its prognostic significance may differ depending on the CRC stage.
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Affiliation(s)
- Younghoo Jo
- Yonsei University College of Medicine, Seoul, South Korea
| | - Jae-Hoon Lee
- Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Eun-Suk Cho
- Department of Radiology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Hye Sun Lee
- Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, South Korea
| | - Su-Jin Shin
- Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Eun Jung Park
- Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Seung Hyuk Baik
- Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Kang Young Lee
- Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Jeonghyun Kang
- Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
- *Correspondence: Jeonghyun Kang,
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SPATA18 Expression Predicts Favorable Clinical Outcome in Colorectal Cancer. Int J Mol Sci 2022; 23:ijms23052753. [PMID: 35269894 PMCID: PMC8910917 DOI: 10.3390/ijms23052753] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 02/26/2022] [Accepted: 02/26/2022] [Indexed: 01/19/2023] Open
Abstract
Dysregulation of mitochondrial quality control has been reported to be associated with cancer and degenerative diseases. SPATA18 (spermatogenesis-associated 18, also known as Mieap) encodes a p53-inducible protein that can induce lysosome-like organelles within mitochondria that eliminate oxidized mitochondrial proteins and has tumor suppressor functions in mitochondrial quality control. In the present study, 268 primary colorectal cancers (CRCs) were evaluated immunohistochemically for SPATA18 expression to assess its predictive utility and its association with cellular proliferation activity. Furthermore, the association with p53 immunoreactivity, a surrogate marker for TP53 mutation, was analyzed. Non-neoplastic colonic mucosa showed cytoplasmic SPATA18 expression. Seventy-two percent of the lesions (193/268) displayed high SPATA18 expression in the cytoplasm of CRC cells. Univariate analyses revealed significant associations between SPATA18 expression and tumor size (p < 0.0001), histological differentiation (p = 0.0017), and lymph node metastasis (p = 0.00039). The log-rank test revealed that patients with SPATA18-high CRCs had significantly better survival than SPATA18-low patients (p < 0.0001). Multivariate Cox hazards regression analysis identified tubular-forming histology (hazard ratio [HR] = 0.25), age < 70 years (HR = 0.50), and SPATA18-high (HR = 0.55) as potential favorable factors. Lymph node metastasis (HR = 1.98) and peritoneal metastasis (HR = 5.45) were cited as potential independent risk factors. Cellular proliferation activity was significantly higher in SPATA18-high tumors. However, no significant correlation was detected between SPATA18 expression and p53 immunoreactivity or KRAS/BRAF mutation status. On the basis of our observations, SPATA18 immunohistochemistry can be used in the prognostication of CRC patients.
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Huang M, He J, Lai W, Liu L, Xu H, Zeng Y, Lan Q, Lin X, Chu Z. Methylated septin 9 gene is an important prognostic marker in stage II and stage III colorectal cancer for evaluating local recurrence or distant metastasis after surgery. BMC Gastroenterol 2022; 22:87. [PMID: 35227194 PMCID: PMC8883666 DOI: 10.1186/s12876-022-02172-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Accepted: 02/16/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Abnormal hypermethylation of the septin 9 gene was an inchoate incident in some cancers. Though latest several researches had paid attention to its value in prognosis, the consequences were not distinctly, especially in colorectal cancer (CRC) with stage II and stage III. PURPOSE The aim of this research was to pick up the prognostic value of the methylated septin 9 gene (mSEPT9) in CRC patients, particularly in TNM stage II-III. METHODS Blood samples before surgery were obtained from 144 CRC patients, of which there were 94 with stage II and stage III. mSEPT9 was considered positive when the cycle number of the peak reaction (Ct) was lower than the threshold value (41.0) for two times during three times PCR test. mSEPT9 and other relative factors of prognosis were estimated by survival analysis. The level of septin 9 in tissues was tested by immunohistochemical (IHC). RESULTS Stage II and stage III patients with mSEPT9 positive (mSEPT9+) had a lower disease-free survival (DFS) rate than those with mSEPT9 negative (mSEPT9-) (2-year DFS rates, 52.1% vs 73.9%, P = 0.014). In multivariate regression analysis, mSEPT9 was also an independent predictor of prognosis (HR = 2.741, P = 0.009). The risk of local recurrence or distant metastasis in CRC patients after surgery was mSEPT9+ with stage III, mSEPT9- with stage III/mSEPT9+ with stage II, and mSEPT9- with stage II (P = 0.001), from highest to lowest. In addition, mSEPT9 was strongly associated with TNM staging, tumor immersion depth, distant metastasis, differentiation degree, vascular invasion and microsatellite. When we explored the associations between septin 9 protein level revealed by IHC and other elements, recurrence/progression (R = - 0.523, P = 0.001), mSEPT9 status (R = - 0.451, P = 0.004) and T stage (R = - 0.375, P = 0.017) showed significant correlations. CONCLUSIONS Positive mSEPT9 is a poor prognostic marker for CRC patients in stage II and III. It is also a powerful complement to TNM staging in predicting postoperative DFS of CRC patients of stage II and III.
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Affiliation(s)
- Mingliang Huang
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Gastrointestinal Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang West Road, Guangzhou, 510120, China
| | - Jiehua He
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.,Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang West Road, Guangzhou, 510120, China
| | - Wei Lai
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Gastrointestinal Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang West Road, Guangzhou, 510120, China
| | - Lu Liu
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Gastrointestinal Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang West Road, Guangzhou, 510120, China
| | - Heyang Xu
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Gastrointestinal Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang West Road, Guangzhou, 510120, China
| | - Yujie Zeng
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Gastrointestinal Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang West Road, Guangzhou, 510120, China
| | - Qiusheng Lan
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Gastrointestinal Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang West Road, Guangzhou, 510120, China
| | - Xiangan Lin
- Department of Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang West Road, Guangzhou, 510120, China.
| | - Zhonghua Chu
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Gastrointestinal Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang West Road, Guangzhou, 510120, China.
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Xu M, Liu Y, Xue T, Ye Q, Xiang J, Liu L, Yan B. Prognostic Implication of Preoperative Serum Albumin to Carcinoembryonic Antigen Ratio in Colorectal Cancer Patients. Technol Cancer Res Treat 2022; 21:15330338221078645. [PMID: 35253553 PMCID: PMC8905062 DOI: 10.1177/15330338221078645] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 01/13/2022] [Accepted: 01/19/2022] [Indexed: 11/23/2022] Open
Abstract
Background: Preoperative serum albumin (ALB) and carcinoembryonic antigen (CEA) were useful prognostic factors in colorectal cancer (CRC); however, the ALB to CEA ratio (ACR) and their individual prognostic efficacies have been less studied. Methods: A retrospective study with 156 CRC patients staged I to IV was performed. The prognostic efficacy of ACR was estimated and subsequently compared with ALB, CEA, and other systemic inflammation markers, including the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR). Differences in progression-free survival (PFS) and overall survival (OS) were determined by Kaplan-Meier (K-M) analysis, and the risk factors for survival were calculated by the Cox proportional hazards model. Results: A total of 31.41% (49 of 156) of patients presented with ACR-low disease, and these patients had tumors with advanced T stages, larger tumor diameters and distant metastases, and a lower LMR. When 5.98 was used as the cut-off point, it had a sensitivity of 58.50% and 61.50% and a specificity of 83.50% and 80.50% for PFS and OS, respectively. ACR displayed a superior prognostic efficacy than individual ALB, CEA and NLR, LMR, and PLR for both PFS and OS (except LMR). Patients in the ACR-low group displayed significantly worse PFS and OS than those in the ACR-high group. Finally, ACR was an independent prognostic factor for both PFS (HR = 0.31, 95% CI: 0.17-0.56, P < .01) and OS (HR = 0.33, 95% CI: 0.16-0.66, P < .01). Conclusions: ACR was a robust prognostic factor in CRC, and patients with a relatively low preoperative ACR would have significantly worse survival.
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Affiliation(s)
- Mingyue Xu
- Department of General Surgery, Hainan Hospital of Chinese PLA General Sanya city of Hainan Province, P.R. China
| | - You Liu
- Department of General Surgery, Hainan Hospital of Chinese PLA General Sanya city of Hainan Province, P.R. China
| | - Tianhui Xue
- Department of General Surgery, Hainan Hospital of Chinese PLA General Sanya city of Hainan Province, P.R. China
| | - Qianwen Ye
- Department of General Surgery, Hainan Hospital of Chinese PLA General Sanya city of Hainan Province, P.R. China
| | - Jia Xiang
- Department of Oncology, Hainan Hospital of Chinese PLA General Hospital, Sanya City of Hainan Province, P.R. China
| | - Long Liu
- Department Traditional Chinese Medicine, Tianyou Hospital of Tongji University, Shanghai, P.R. China
| | - Bing Yan
- Department of Oncology, Hainan Hospital of Chinese PLA General Hospital, Sanya City of Hainan Province, P.R. China
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Zhou S, Zhang M, Zhou C, Meng Y, Yang H, Ye W. FLVCR1 Predicts Poor Prognosis and Promotes Malignant Phenotype in Esophageal Squamous Cell Carcinoma via Upregulating CSE1L. Front Oncol 2021; 11:660955. [PMID: 33842377 PMCID: PMC8027484 DOI: 10.3389/fonc.2021.660955] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Accepted: 03/10/2021] [Indexed: 01/19/2023] Open
Abstract
Objective Dysregulation of feline leukemia virus subgroup C receptor 1(FLVCR1) expression has been investigated in several tumors. However, the expression and role of FLVCR1 in esophageal squamous cell carcinoma (ESCC) remain largely unknown. Methods FLVCR1 expression in tissues was measured by immunohistochemical staining (IHC). Celigo assay, MTT assay, colony formation, caspase 3/7 activity analysis, wound healing assay, Transwell migration, and invasion assay were applied to assess the effects of FLVCR1 on ESCC tumorigenesis. Coimmunoprecipitation (Co-IP) and liquid chromatography-mass spectrometry (LC-MS) were used to identify protein interactions with FLVCR1. An in vivo imaging system (IVIS) was used to investigate the functions of FLVCR1 on the growth and metastatic capability of ESCC cells in a xenograft model and a tail vein metastasis model. Results Elevated expression of FLVCR1 was detected in ESCC tissues and predicted poor survival. Upregulated FLVCR1 was positively correlated with lymph node metastasis (N stage) and late tumor-node-metastasis (TNM) stage. FLVCR1 knockdown inhibited cell proliferation and colony formation ability, induced cell apoptosis, and repressed cell migration and invasion of ESCC in vitro. Inhibition of FLVCR1 markedly repressed tumorigenicity and metastasis of ESCC cells in vivo. Mechanistically, chromosome segregation 1–like (CSE1L) was identified to interact with FLVCR1 using a Co-IP assay. Moreover, the inhibitory effect of FLVCR1 knockdown on proliferation and migration was counteracted by the exogenous expression of CSE1L. Conclusion FLVCR1 plays a pivotal role in ESCC cell survival, growth, and migration. These functions may be partially dependent upon the protein interaction between FLVCR1 and CSE1L. In addition, FLVCR1 can be applied as a clinical prognostic marker for patients with ESCC.
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Affiliation(s)
- Suna Zhou
- Laboratory of Cellular and Molecular Radiation Oncology, The Affiliated Taizhou Hospital, Wenzhou Medical University, Taizhou, China.,Department of Radiation Oncology, The Affiliated Taizhou Hospital, Wenzhou Medical University, Taizhou, China.,Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Taizhou, China
| | - Mingxin Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Xi'an Medical University, Xi'an, China
| | - Chao Zhou
- Laboratory of Cellular and Molecular Radiation Oncology, The Affiliated Taizhou Hospital, Wenzhou Medical University, Taizhou, China.,Department of Radiation Oncology, The Affiliated Taizhou Hospital, Wenzhou Medical University, Taizhou, China.,Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Taizhou, China
| | - Yinnan Meng
- Laboratory of Cellular and Molecular Radiation Oncology, The Affiliated Taizhou Hospital, Wenzhou Medical University, Taizhou, China.,Department of Radiation Oncology, The Affiliated Taizhou Hospital, Wenzhou Medical University, Taizhou, China.,Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Taizhou, China
| | - Haihua Yang
- Laboratory of Cellular and Molecular Radiation Oncology, The Affiliated Taizhou Hospital, Wenzhou Medical University, Taizhou, China.,Department of Radiation Oncology, The Affiliated Taizhou Hospital, Wenzhou Medical University, Taizhou, China.,Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Taizhou, China
| | - Wenguang Ye
- Department of Gastroenterology, The Affiliated Taizhou Hospital, Wenzhou Medical University, Taizhou, China
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Fan S, Cui X, Liu C, Li X, Zheng L, Song Q, Qi J, Ma W, Ye Z. CT-Based Radiomics Signature: A Potential Biomarker for Predicting Postoperative Recurrence Risk in Stage II Colorectal Cancer. Front Oncol 2021; 11:644933. [PMID: 33816297 PMCID: PMC8017337 DOI: 10.3389/fonc.2021.644933] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 02/24/2021] [Indexed: 12/27/2022] Open
Abstract
Objective: To evaluate whether a radiomics signature could improve stratification of postoperative risk and prediction of chemotherapy benefit in stage II colorectal cancer (CRC) patients. Material and Methods: This retrospective study enrolled 299 stage II CRC patients from January 2010 to December 2015. Based on preoperative portal venous-phase CT scans, radiomics features were generated and selected to build a radiomics score (Rad-score) using the Least Absolute Shrinkage and Selection Operator (LASSO) method. The minority group was balanced by the synthetic minority over-sampling technique (SMOTE). Predictive models were built with the Rad-score and clinicopathological factors, and the area under the curve (AUC) was used to evaluate their performance. A nomogram was also constructed for predicting 3-year disease-free survival (DFS). The performance of the nomogram was assessed with a concordance index (C-index) and calibration plots. Results: Overall, 114 features were selected to construct the Rad-score, which was significantly associated with the 3-year DFS. Multivariate analysis demonstrated that the Rad-score, CA724 level, mismatch repair status, and perineural invasion were independent predictors of recurrence. Results showed that the Rad-score can classify patients into high-risk and low-risk groups in the training cohort (AUC 0.886) and the validation cohort (AUC 0.874). On this basis, a nomogram that integrated the Rad-score and clinical variables demonstrated superior performance (AUC 0.954, 0.906) than the clinical model alone (AUC 0.765, 0.705) in the training and validation cohorts, respectively. The C-index of the nomogram was 0.872, and the performance was acceptable. Conclusion: Our radiomics-based model can reliably predict recurrence risk in stage II CRC patients and potentially provide complementary prognostic value to the traditional clinicopathological risk factors for better identification of patients who are most likely to benefit from adjuvant therapy. The proposed nomogram promises to be an effective tool for personalized postoperative surveillance for stage II CRC patients.
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Affiliation(s)
- Shuxuan Fan
- Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Centre of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Xiaonan Cui
- Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Centre of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Chunli Liu
- School of Electronics and Information Engineering, TianGong University, Tianjin, China
| | - Xubin Li
- Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Centre of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Lei Zheng
- Department of Colorectal Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Centre of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Qian Song
- Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Centre of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Jin Qi
- Department of Cancer Physiology, H. Lee Moffitt Cancer Center, Tampa, FL, United States
| | - Wenjuan Ma
- Department of Breast Imaging, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Centre of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Zhaoxiang Ye
- Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Centre of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
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Nagano-Matsuo A, Inoue S, Koshino A, Ota A, Nakao K, Komura M, Kato H, Naiki-Ito A, Watanabe K, Nagayasu Y, Hosokawa Y, Takiguchi S, Kasugai K, Kasai K, Inaguma S, Takahashi S. PBK expression predicts favorable survival in colorectal cancer patients. Virchows Arch 2021; 479:277-284. [PMID: 33638656 DOI: 10.1007/s00428-021-03062-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Revised: 02/05/2021] [Accepted: 02/15/2021] [Indexed: 01/02/2023]
Abstract
Colorectal cancer (CRC) is one of the most common gastrointestinal cancers worldwide with high morbidity and mortality rates. The discovery of small molecule anticancer reagents has significantly affected cancer therapy. However, the anticancer effects of these therapies are not sufficient to completely cure CRC. PDZ-binding kinase (PBK) was initially identified as a mitotic kinase for mitogen-activated protein kinase and is involved in cytokinesis and spermatogenesis. Aberrant expression of PBK has been reported to be closely associated with malignant phenotypes of many cancers and/or patient survival. However, the expression of PBK and its association to patient survival in CRC have not been fully elucidated. In the present study, 269 primary CRCs were evaluated immunohistochemically for PBK expression to assess its ability as a prognostic factor. CRC tumor cells variably expressed PBK (range, 0-100%; median, 32%) in the nucleus and cytoplasm. Univariate analyses identified a significant inverse correlation between PBK expression and pT stage (P<0.0001). Furthermore, patients carrying CRC with higher PBK expression showed significantly favorable survival (P=0.0094). Multivariate Cox proportional hazards regression analysis revealed high PBK expression (HR, 0.52; P=0.015) as one of the potential favorable factors for CRC patients. PBK expression showed significant correlation to Ki-67 labeling indices (ρ=0.488, P<0.0001). In vitro, the PBK inhibitor OTS514 suppressed cellular proliferation of CRC cells with PBK expression through downregulation of P-ERK and induction of apoptosis. These results suggest that PBK-targeting therapeutics may be useful for the treatment of PBK-expressing CRC patients.
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Affiliation(s)
- Aya Nagano-Matsuo
- Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Satoshi Inoue
- Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Akira Koshino
- Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Akinobu Ota
- Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Kenju Nakao
- Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Masayuki Komura
- Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Hiroyuki Kato
- Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Aya Naiki-Ito
- Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Kawori Watanabe
- Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Yuko Nagayasu
- Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Yoshitaka Hosokawa
- Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Shuji Takiguchi
- Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Kunio Kasugai
- Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Kenji Kasai
- Department of Pathology, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Shingo Inaguma
- Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. .,Department of Pathology, Aichi Medical University School of Medicine, Nagakute, Japan. .,Department of Pathology, Nagoya City East Medical Center, Nagoya, Japan. .,Educational Research Center for Advanced Medicine, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
| | - Satoru Takahashi
- Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
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Koshino A, Inoue S, Sugimura-Nagata A, Nishiyama T, Murakami H, Ito H, Riku M, Inoko A, Ebi M, Ogasawara N, Tsuzuki T, Kasugai K, Kasai K, Inaguma S. High phospho-histone H3 expression uniquely predicts favorable survival among four markers of cellular proliferation in colorectal cancer. Pathol Int 2021; 71:316-324. [PMID: 33631042 DOI: 10.1111/pin.13084] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Accepted: 01/31/2021] [Indexed: 12/15/2022]
Abstract
Colorectal cancer (CRC) is one of the most frequent gastrointestinal cancers worldwide, with high morbidity and mortality rates. Despite numerous attempts to identify prognostic markers for the CRC patients, the significance of the association of cellular proliferation markers with survival is controversial. Here we used immunohistochemistry to detect four markers of cellular proliferation expressed in primary CRC tissue specimens (n = 269) to assess their potential to serve as prognostic factors. CRC cells variably expressed phospho-histone H3 (PHH3) (range, 0-76 per high-powered field (HPF); median, 7 per HPF), cyclin A (CCNA) (range, 11.3-73.7%; median, 32%), geminin (GMNN) (range, 7.8-82.0%; median, 37.1%), and marker of proliferation Ki-67 (MKI67) (range, 4.9-96.6%; median, 49.6%). Among them, patients with PHH3-high (≥7 per HPF) tumors uniquely experienced significantly longer 5-year survival than those with PHH3-low (≤6 per HPF) (81.8% vs. 65.5%; P = 0.0047). Multivariable Cox hazards regression analysis identified PHH3-high (hazard ratio, 0.54; 95% confidence interval, 0.31-0.92; P = 0.025) as potential favorable factors. PHH3 levels inversely associated with pT stage (P < 0.0001) and were significantly and inversely associated with tumor diameter (ρ = -0.314, P < 0.0001). These findings support the use of PHH3 immunohistochemistry for predicting the prognoses of patients with CRC.
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Affiliation(s)
- Akira Koshino
- Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Aichi, Japan
| | - Satoshi Inoue
- Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Aichi, Japan
| | - Akane Sugimura-Nagata
- Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Aichi, Japan
| | - Takeshi Nishiyama
- Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan
| | - Hideki Murakami
- Department of Pathology, Aichi Medical University School of Medicine, Aichi, Japan
| | - Hideaki Ito
- Department of Pathology, Aichi Medical University School of Medicine, Aichi, Japan
| | - Miho Riku
- Department of Pathology, Aichi Medical University School of Medicine, Aichi, Japan
| | - Akihito Inoko
- Department of Pathology, Aichi Medical University School of Medicine, Aichi, Japan
| | - Masahide Ebi
- Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Aichi, Japan
| | - Naotaka Ogasawara
- Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Aichi, Japan
| | - Toyonori Tsuzuki
- Surgical Pathology, Aichi Medical University School of Medicine, Aichi, Japan
| | - Kunio Kasugai
- Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Aichi, Japan
| | - Kenji Kasai
- Department of Pathology, Aichi Medical University School of Medicine, Aichi, Japan
| | - Shingo Inaguma
- Department of Pathology, Aichi Medical University School of Medicine, Aichi, Japan.,Department of Pathology, Nagoya City East Medical Center, Aichi, Japan.,Educational Research Center for Advanced Medicine, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan
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Su P, Lai W, Liu L, Zeng Y, Xu H, Lan Q, Chu Z, Chu Z. Mesenchymal and Phosphatase of Regenerating Liver-3 Status in Circulating Tumor Cells May Serve as a Crucial Prognostic Marker for Assessing Relapse or Metastasis in Postoperative Patients With Colorectal Cancer. Clin Transl Gastroenterol 2020; 11:e00265. [PMID: 33512811 PMCID: PMC7743843 DOI: 10.14309/ctg.0000000000000265] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Accepted: 10/12/2020] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Circulating tumor cells (CTCs) and phosphatase of regenerating liver-3 (PRL-3) have been considered to be significant prognostic indicators in metastatic colorectal cancer (CRC). This study discusses the prognostic significance of mesenchymal CTCs with PRL-3 (M+ PRL-3+ CTCs) in postoperative patients with CRC. METHODS We detected CTC subtypes (including epithelial CTCs, biphenotypic epithelial/mesenchymal CTCs, and mesenchymal CTCs) and PRL-3 in CTCs from the peripheral blood samples of 156 patients. Receiver operating characteristic curve analysis, Kaplan-Meier analysis, and Cox proportional hazards regression analysis were performed to identify the prognostic value of mesenchymal CTCs with PRL-3+. Immunohistochemistry was used to detect the expression of PRL-3 in tumor tissues from some of the patients to explore the connection between CTCs and tissues. RESULTS All CTCs were positive in all samples, both mesenchymal CTCs and PRL-3-positive cells. The count of mesenchymal and PRL-3+ CTCs was significantly associated with recurrence, and the optimal cutoff value was 2 (area under the curve = 0.690, P < 0.001). In addition, these patients had a significantly shorter median disease-free survival than those who did not fulfill the criteria (8.5 vs 24 months, P < 0.001) according to multivariable and multinomial logistic regression. Immunohistochemistry was applied to explore the associations between PRL-3 expression and significant prognostic risk factors, including recurrence (R = 0.566; P < 0.001), and M+ PRL-3+ status in CTCs (R = 0.452; P = 0.001). DISCUSSION The status of M+ PRL-3+ in CTCs may serve as a crucial prognostic marker for assessing clinical outcomes in CRC.
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Affiliation(s)
- PengWei Su
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Gastrointestinal Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Wei Lai
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Gastrointestinal Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Lu Liu
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Gastrointestinal Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yujie Zeng
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Gastrointestinal Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Heyang Xu
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Gastrointestinal Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Qiusheng Lan
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Gastrointestinal Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Ziqiang Chu
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Gastrointestinal Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhonghua Chu
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Gastrointestinal Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
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12
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Lee MW, Kim JS, Kim JY, Lee KH. Prognostic Factor and Survival Benefit of Adjuvant Chemotherapy in Stage IIA Colon Cancer. Ann Coloproctol 2020; 37:35-43. [PMID: 32972104 PMCID: PMC7989565 DOI: 10.3393/ac.2020.09.03] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Accepted: 09/03/2020] [Indexed: 01/04/2023] Open
Abstract
Purpose There is no clear evidence of the benefit of adjuvant chemotherapy (AC) in stage IIA colon cancer. Therefore, we aimed to evaluate the prognostic factors and survival benefit of AC in this disease. Methods A retrospective data collection for patients who underwent radical surgery for colon cancer between January 2008 and December 2015 was undertaken. The cohort was divided into the no-AC and AC groups. Results We included 227 patients with stage IIA colon cancer in our study cohort, including 67 and 160 patients in the no-AC and AC groups, respectively. The number of retrieved lymph nodes and the presence of tumor complications as obstruction or perforation were independent risk factors for survival. In the no-AC group, there was a significant difference in survival according to the number of retrieved lymph nodes. In the AC group, there were significant differences in survival according to sidedness and preoperative carcinoembryonic antigen (CEA). There was no significant difference in survival between the no-AC and the AC groups. Conclusion The number of retrieved lymph nodes and the presence of tumor complications were prognostic factors for stage IIA colon cancer but lymphovascular and perineural invasion were not. Sidedness and preoperative CEA could be used as factors to predict the benefit of adjuvant chemotherapy. Currently, it is believed that there is no benefit of AC for stage IIA colon cancer. Further studies are needed to determine the survival benefit of adjuvant chemotherapy in stage IIA colon cancer.
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Affiliation(s)
- Mok-Won Lee
- Department of Surgery, Chungnam National University Hospital, Daejeon, Korea
| | - Jin-Su Kim
- Department of Surgery, Chungnam National University Hospital, Daejeon, Korea
| | - Ji-Yeon Kim
- Department of Surgery, Chungnam National University Hospital, Daejeon, Korea
| | - Kyung-Ha Lee
- Department of Surgery, Chungnam National University Hospital, Daejeon, Korea
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13
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Fan S, Li X, Cui X, Zheng L, Ren X, Ma W, Ye Z. Computed Tomography-Based Radiomic Features Could Potentially Predict Microsatellite Instability Status in Stage II Colorectal Cancer: A Preliminary Study. Acad Radiol 2019; 26:1633-1640. [PMID: 30929999 DOI: 10.1016/j.acra.2019.02.009] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Revised: 02/11/2019] [Accepted: 02/12/2019] [Indexed: 12/20/2022]
Abstract
RATIONALE AND OBJECTIVES To investigate whether quantitative radiomics features extracted from computed tomography (CT) can predict microsatellite instability (MSI) status in an Asian cohort of patients with stage Ⅱ colorectal cancer (CRC). MATERIALS AND METHODS This retrospective study was approved by our institutional review board, and the informed consent requirement was waived. From March 2016 to March 2018, 119 Chinese patients with pathologically confirmed stage Ⅱ CRC, available MSI status, and preoperative contrast-enhanced CT images were included in this study. Clinical and pathological information was obtained from the institutional database. The radiomics features were extracted from portal venous-phase CT images of segmented volumes of each entire primary tumor by using Matrix Laboratory (MATLAB), and radiomics signatures were generated using the least absolute shrinkage and selection operator logistic regression model. The minority group was balanced via synthetic minority over-sampling technique method. The association between the clinicopathologic characteristics and MSI status was assessed using Student's t test, Chi-square, or Fisher's exact test. The predictive efficacy of MSI status using radiomics features, clinical factors (including age, gender, CT-reported tumor location, differentiation degree of tumor, smoking history, hypertension history, family history of cancer, diabetes history, level of the Ki-67 expression, and laboratory analysis) and the combined models were evaluated, respectively. Predictive performance was evaluated by the area under receiver operating characteristic curve, accuracy, sensitivity, and specificity. RESULTS MSI status was significantly associated with tumor location (p = 0.043); differentiation degree of tumor (p < 0.0001), hypertension history (p = 0.012), and the level of the Ki-67 expression (p = 0.015). Six radiomics features and 11 clinical characteristics were selected for predicting MSI status. The model that used the combination of clinical factors and radiomics features achieved the overall best performance than using either of the two features alone, yielding the area under the curve, sensitivity, and specificity of 0.752, 0.663, 0.841 for the combined model, 0.598, 0.371, 0.825 for clinical factors alone, and 0.688, 0.517, 0.858 for radiomics features alone, respectively. CONCLUSION CT-based radiomic features of stage Ⅱ CRC are associated with MSI status. Combining analysis of clinical features and CT features could improve predictive efficacy and could potentially select the patients for individualized therapy noninvasively.
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Affiliation(s)
- Shuxuan Fan
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin 300060, China
| | - Xubin Li
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin 300060, China
| | - Xiaonan Cui
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin 300060, China
| | - Lei Zheng
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin 300060, China
| | - Xiaoyi Ren
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin 300060, China
| | - Wenjuan Ma
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin 300060, China.
| | - Zhaoxiang Ye
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin 300060, China.
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14
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Téllez T, Abitei C, Padilla-Ruiz MDC, Rivas-Ruiz F, Fúnez R, Pereda T, Rodrigo I, Alcaide J, Baré ML, Morales Suárez-Varela MM, Zabalza I, Sánchez Del Charco M, Borrero Martín JJ, García Del Moral R, Escobar A, Quintana JM, Aguirre U, Redondo M. Biological and prognostic differences between symptomatic colorectal carcinomas and those detected by screening. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2019; 45:1876-1881. [PMID: 31189513 DOI: 10.1016/j.ejso.2019.05.027] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Revised: 05/16/2019] [Accepted: 05/23/2019] [Indexed: 11/21/2022]
Abstract
INTRODUCTION Few studies have been conducted to establish the relationship between colorectal cancer screening programmes and survival adjusting by stage and, to determine whether there are differences, at a biological level, between the tumours of asymptomatic and symptomatic patients. Accordingly, the aim of this study is to evaluate clinical, biological and survival differences between symptomatic colorectal tumours and those detected by screening. STUDY METHOD A prospective cohort study was performed of patients subjected to surgical intervention during the period 2010-2012, at different hospitals in Spain. In every case, clinical, pathological, biological and survival-related variables were obtained. RESULTS A total of 2634 patients from the CARESS-CCR cohort were analysed; of these, 220 were diagnosed through screening. The asymptomatic patients were younger, had a higher Body Mass Index (BMI), a lower degree of perineural invasion and a less advanced T stage and nodular stage, and the tumour was frequently located on the right side of the colon. All of these differences were statistically significant. The serum tumour marker carbohydrate antigen 19.9 (CA 19.9) was found more frequently in the symptomatic patients (p < 0.05). However, no significant differences were found regarding the markers of tumour biology: Ki67 (proliferation), CD105 (angiogenesis) and the Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay (apoptosis). The patients with asymptomatic tumours had a lower mortality at five years than those diagnosed presenting symptoms. CONCLUSIONS The detection method employed influenced the survival of patients with colorectal cancer and there were no significant biological differences between the study groups.
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Affiliation(s)
- Teresa Téllez
- Research Unit, Costa del Sol Hospital, Research Network on Health Services in Chronic Diseases (REDISSEC), University of Málaga, Marbella, Spain; Instituto de Investigación Biomedica de Málaga (IBIMA), Spain
| | - Cristina Abitei
- Servicio de Anatomía Patológica, Hospital Costa del Sol, Marbella, Spain
| | - María Del Carmen Padilla-Ruiz
- Research Unit, Costa del Sol Hospital, Research Network on Health Services in Chronic Diseases (REDISSEC), University of Málaga, Marbella, Spain
| | - Francisco Rivas-Ruiz
- Research Unit, Costa del Sol Hospital, Research Network on Health Services in Chronic Diseases (REDISSEC), University of Málaga, Marbella, Spain
| | - Rafael Fúnez
- Instituto de Investigación Biomedica de Málaga (IBIMA), Spain; Servicio de Anatomía Patológica, Hospital Costa del Sol, Marbella, Spain
| | - Teresa Pereda
- Instituto de Investigación Biomedica de Málaga (IBIMA), Spain; Servicio de Anatomía Patológica, Hospital Costa del Sol, Marbella, Spain
| | - Isabel Rodrigo
- Servicio de Anatomía Patológica, Hospital Costa del Sol, Marbella, Spain
| | - Julia Alcaide
- Instituto de Investigación Biomedica de Málaga (IBIMA), Spain; Research Unit, Costa del Sol Hospital, Research Network on Health Services in Chronic Diseases (REDISSEC), University of Málaga, Department of Oncohaematology, Costa del Sol Hospital, Marbella, Spain
| | - María Luisa Baré
- Clinical Epidemiology and Cancer Screening, Corporació Sanitaria ParcTaulí, REDISSEC, Sabadell, Spain
| | | | - Iñaki Zabalza
- Servicio de Anatomía Patológica, Hospital de Galdakao, Galdakao, Vizcaya, Spain
| | | | | | - Raimundo García Del Moral
- Departamento de Patología, Complejo Hospitalario de Granada, Instituto de Investigación Biosanitaria y Universidad de Granada, Granada, Spain
| | - Antonio Escobar
- Research Unit, Basurto University Hospital, REDISSEC, Bilbao, Spain
| | - José María Quintana
- Research Unit, Galdakao-Usansolo Hospital, Galdakao-Usansolo Hospital, REDISSEC, Spain
| | - Urko Aguirre
- Research Unit, Galdakao-Usansolo Hospital, Galdakao-Usansolo Hospital, REDISSEC, Spain
| | - Maximino Redondo
- Research Unit, Costa del Sol Hospital, Research Network on Health Services in Chronic Diseases (REDISSEC), University of Málaga, Marbella, Spain; Instituto de Investigación Biomedica de Málaga (IBIMA), Spain.
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15
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Cai D, Huang ZH, Yu HC, Wang XL, Bai LL, Tang GN, Peng SY, Li YJ, Huang MJ, Cao GW, Wang JP, Luo YX. Prognostic value of preoperative carcinoembryonic antigen/tumor size in rectal cancer. World J Gastroenterol 2019; 25:4945-4958. [PMID: 31543685 PMCID: PMC6737319 DOI: 10.3748/wjg.v25.i33.4945] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2019] [Revised: 04/04/2019] [Accepted: 05/18/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Carcinoembryonic antigen (CEA) is a commonly used biomarker in colorectal cancer. However, controversy exists regarding the insufficient prognostic value of preoperative serum CEA alone in rectal cancer. Here, we combined preoperative serum CEA and the maximum tumor diameter to correct the CEA level, which may better reflect the malignancy of rectal cancer.
AIM To assess the prognostic impact of preoperative CEA/tumor size in rectal cancer.
METHODS We retrospectively reviewed 696 stage I to III rectal cancer patients who underwent curative tumor resection from 2007 to 2012. These patients were randomly divided into two cohorts for cross-validation: training cohort and validation cohort. The training cohort was used to generate an optimal cutoff point and the validation cohort was used to further validate the model. Maximally selected rank statistics were used to identify the optimum cutoff for CEA/tumor size. The Kaplan-Meier method and log-rank test were used to plot the survival curve and to compare the survival data. Univariate and multivariate Cox regression analyses were used to determine the prognostic value of CEA/tumor size. The primary and secondary outcomes were overall survival (OS) and disease-free survival (DFS), respectively.
RESULTS In all, 556 patients who satisfied both the inclusion and exclusion criteria were included and randomly divided into the training cohort (2/3 of 556, n = 371) and the validation cohort (1/3 of 556, n = 185). The cutoff was 2.429 ng/mL per cm. Comparison of the baseline data showed that high CEA/tumor size was correlated with older age, high TNM stage, the presence of perineural invasion, high CEA, and high carbohydrate antigen 19-9 (CA 19-9). Kaplan-Meier curves showed a manifest reduction in 5-year OS (training cohort: 56.7% vs 81.1%, P < 0.001; validation cohort: 58.8% vs 85.6%, P < 0.001) and DFS (training cohort: 52.5% vs 71.9%, P = 0.02; validation cohort: 50.3% vs 79.3%, P = 0.002) in the high CEA/tumor size group compared with the low CEA/tumor size group. Univariate and multivariate analyses identified CEA/tumor size as an independent prognostic factor for OS (training cohort: hazard ratio (HR) = 2.18, 95% confidence interval (CI): 1.28-3.73, P = 0.004; validation cohort: HR = 4.83, 95%CI: 2.21-10.52, P < 0.001) as well as DFS (training cohort: HR = 1.47, 95%CI: 0.93-2.33, P = 0.096; validation cohort: HR = 2.61, 95%CI: 1.38-4.95, P = 0.003).
CONCLUSION Preoperative CEA/tumor size is an independent prognostic factor for patients with stage I-III rectal cancer. Higher CEA/tumor size is associated with worse OS and DFS.
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Affiliation(s)
- Du Cai
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease (Supported by National Key Clinical Discipline), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
| | - Zeng-Hong Huang
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease (Supported by National Key Clinical Discipline), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
- Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, Sacramento, CA 95817, United States
| | - Hui-Chuan Yu
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease (Supported by National Key Clinical Discipline), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
| | - Xiao-Lin Wang
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease (Supported by National Key Clinical Discipline), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
| | - Liang-Liang Bai
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease (Supported by National Key Clinical Discipline), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
| | - Guan-Nan Tang
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease (Supported by National Key Clinical Discipline), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
| | - Shao-Yong Peng
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease (Supported by National Key Clinical Discipline), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
| | - Ying-Jie Li
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease (Supported by National Key Clinical Discipline), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
| | - Mei-Jin Huang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
| | - Guang-Wen Cao
- Department of Epidemiology, Second Military Medical University, Shanghai 200433, China
| | - Jian-Ping Wang
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease (Supported by National Key Clinical Discipline), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
| | - Yan-Xin Luo
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease (Supported by National Key Clinical Discipline), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
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16
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Li H, Zhao S, Jing Z, Li J, Shuanying Y, Zhang N. Combination of D-dimer and carcinoembryonic antigen levels as a predictive and prognostic biomarker in advanced colorectal cancer patients. J Cell Biochem 2019; 120:8086-8092. [PMID: 30592316 DOI: 10.1002/jcb.28087] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Accepted: 10/29/2018] [Indexed: 01/24/2023]
Abstract
In view of the controversial findings on the utility of D-dimer and carcinoembryonic antigen (CEA) as biomarkers in advanced colorectal cancer (CRC), we evaluated the predictive and prognostic value of the D-dimer and CEA levels in unresectable advanced CRC patients treated with first-line chemotherapy. A total of 57 previously untreated patients with advanced CRC were enrolled. We assessed both plasma D-dimer and CEA levels at the start (D1 and CEA1) and after two cycles (D2 and CEA2) of chemotherapy. Based on the respective optimal cut-off values of 0.8 and 5.0 ng/mL for D1 and CEA1, respectively, patients were divided into low and high D-dimer or CEA groups. The results show that D1 and CEA1 levels were correlated (r = 0.392, P = 0.003). Mean CEA2 was reduced by 26.24 ng/mL in patients with partial response and stable disease and increased by 165.95 ng/mL in patients with progressive disease relative to the CEA1 level (P < 0.001). However, no correlation was evident between changes in the D-dimer levels and chemotherapy response (P = 0.441). The overall survival (OS) of patients with high D1 was shorter than that of patients with low D1 (median OS, 16 vs 29 months, P = 0.009). Multivariate analyses further demonstrated that D1 (P = 0.042) and chemotherapy response (P = 0.016), but not CEA, were independent prognostic factors for OS in advanced CRC. Taken together, our result found that changes in CEA levels may serve as a predictive biomarker of the chemotherapy response and baseline D-dimer levels as a prognostic biomarker of OS in patients with advanced CRC.
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Affiliation(s)
- Huiping Li
- Department of Respiratory Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.,Department of Pancreatitis Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Shuangshuang Zhao
- Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang, China
| | - Zhao Jing
- Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang, China
| | - Juan Li
- Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang, China
| | - Yang Shuanying
- Department of Respiratory Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Ni Zhang
- Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang, China
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17
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Redondo M, Abitei C, Téllez T, Fúnez R, Pereda T, Rodrigo I, Betancourt AM, García-Aranda M, Rueda A, Martínez García RC, Morales Suarez-Varela MM, Zabalza I, Sánchez Del Charco M, Borrero Martín JJ, García Del Moral R, Escobar A, Quintana J, Rivas-Ruiz F. Clinical-pathological characteristics and short-term follow-up associated with proliferation, apoptosis and angiogenesis in a prospective cohort of patients with colorectal tumours. Tumour Biol 2019; 42:1010428319835684. [PMID: 30957671 DOI: 10.1177/1010428319835684] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
We investigate the clinical and pathological features related to variations in colorectal tumour apoptosis, proliferation and angiogenesis and the influence of the latter in short-term mortality (2 years); 551 tumour samples from a prospective cohort of patients with colorectal cancer were examined and tumour biology markers were determined as follows: percentage of apoptotic cells, by the terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling technique; Ki-67 antigen, as a cell proliferation marker and density of microvessels (as a marker of angiogenesis). An increase in the percentage of cellular apoptosis is significantly related to the presence of poorly differentiated tumours, with vascular invasion (p < 0.001). The CD105 angiogenesis marker is not related to any clinical-pathological parameter except that of higher frequency in older patients (p = 0.03). Ki-67 is more frequently expressed in tumours with less nervous invasion (p = 0.05). Neither apoptosis nor angiogenesis present any significant association with short-term survival. The only marker clearly related to 2-year survival is Ki-67, which is shown to be a good prognostic factor in the multivariate analysis (hazard ratio = 0.49; 95% confidence interval = 0.27-0.90). Therefore, in a prospective cohort of colorectal cancer patients, only Ki-67 is a marker of good prognosis in short-term follow-up.
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Affiliation(s)
- Maximino Redondo
- 1 Unidad de Investigación, Hospital Costa del Sol, REDISSEC, Marbella, España
| | - Cristina Abitei
- 2 Servicio de Anatomía Patológica, Hospital Costa del Sol, Marbella, España
| | - Teresa Téllez
- 1 Unidad de Investigación, Hospital Costa del Sol, REDISSEC, Marbella, España
| | - Rafael Fúnez
- 2 Servicio de Anatomía Patológica, Hospital Costa del Sol, Marbella, España
| | - Teresa Pereda
- 2 Servicio de Anatomía Patológica, Hospital Costa del Sol, Marbella, España
| | - Isabel Rodrigo
- 2 Servicio de Anatomía Patológica, Hospital Costa del Sol, Marbella, España
| | - Ana M Betancourt
- 2 Servicio de Anatomía Patológica, Hospital Costa del Sol, Marbella, España
| | | | - Antonio Rueda
- 1 Unidad de Investigación, Hospital Costa del Sol, REDISSEC, Marbella, España
- 3 Servicio de Oncología, Hospital Costa del Sol, Marbella, España
| | | | - María Manuela Morales Suarez-Varela
- 5 Unidad de Salud Pública, Higiene y Sanidad Ambiental, Departamento de Medicina Preventiva y Salud Pública, Universitat de Valencia, CIBER Epidemiología y Salud Pública (CIBERESP), Valencia, España
| | - Iñaki Zabalza
- 6 Servicio de Anatomía Patológica, Hospital de Galdakao, Galdakao, España
| | | | | | - Raimundo García Del Moral
- 9 Departamento de Patología, Complejo Hospitalario de Granada, Instituto de Investigación Biosanitaria y Universidad de Granada, Granada, España
| | - Antonio Escobar
- 10 Unidad de Investigación, Hospital Universitario de Basurto, REDISSEC, Vizcaya, España
| | - JoséMaría Quintana
- 11 Unidad de Investigación, Hospital Universitario de Galdakao, REDISSEC, Galdakao, España
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18
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Guo H, Qi RQ, Sheng J, Liu C, Ma H, Wang HX, Li JH, Gao XH, Wan YS, Chen HD. MiR-155, a potential serum marker of extramammary Paget's disease. BMC Cancer 2018; 18:1078. [PMID: 30458743 PMCID: PMC6247506 DOI: 10.1186/s12885-018-4994-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Accepted: 10/24/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Extramammary Paget's disease (EMPD), a rare skin malignancy with non-specific manifestations, is often misdiagnosed as eczema of scrotum or tinea cruris. Although the diagnosis of EMPD could be confirmed by biopsy, it can be delayed as patients are reluctant to receive invasive operations. Herein, we investigated the serum miRNA expressions of EMPD patients and compared to that of the eczema of scrotum or tinea cruris patients as well as health volunteers for potential diagnostic markers for EMPD. METHODS Altogether 45 subjects including 16 patients diagnosed with EMPD, 12 patients diagnosed with eczema of scrotum or tinea cruris and 17 healthy volunteers were enrolled in this study. Serum from all of subjects were collected to identify miRNAs (by miRNA array global normalization, RT-PCR validation, and receiver operating characteristic curve analysis) that could be potential diagnostic markers for EMPD. RESULTS The miRNA array analyses revealed that the expressions of 37 miRNAs from the EMPD patients were different (change ≥4-fold) from health volunteers. Among these miRNAs, the expression of miR-155 was significantly increased (p < 0.01) in the EMPD patients as compared with that of the health volunteers and the eczema of scrotum or the tinea cruris patients (no difference between these two control groups). In addition, receiver operating characteristic (ROC) curve analysis showed that diagnostic capacities (defined as the area under curve of ROC) of miR-155 are 0.85 (as compared with health volunteers group) and 0.81 (as compared with the eczema of scrotum or the tinea cruris patients group), respectively. CONCLUSION The serum miRNA expression of gene miR-155 in the EMPD patients was differentiated from that of other subjects warranting further validation of miR-155 as a diagnostic marker of EMPD.
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Affiliation(s)
- Hao Guo
- Department of Dermatology, No.1 Hospital of China Medical University, 155N. Nanjing Street, Shenyang, 110001, People's Republic of China
| | - Rui-Qun Qi
- Department of Dermatology, No.1 Hospital of China Medical University, 155N. Nanjing Street, Shenyang, 110001, People's Republic of China
| | - Jie Sheng
- Department of Anesthesiology, No.1 Hospital of China Medical University, 155N. Nanjing Street, Shenyang, 110001, People's Republic of China
| | - Chang Liu
- Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, 02881, USA
| | - Hang Ma
- Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, 02881, USA
| | - He-Xiao Wang
- Department of Dermatology, No.1 Hospital of China Medical University, 155N. Nanjing Street, Shenyang, 110001, People's Republic of China
| | - Jiu-Hong Li
- Department of Dermatology, No.1 Hospital of China Medical University, 155N. Nanjing Street, Shenyang, 110001, People's Republic of China
| | - Xing-Hua Gao
- Department of Dermatology, No.1 Hospital of China Medical University, 155N. Nanjing Street, Shenyang, 110001, People's Republic of China
| | - Yin-Sheng Wan
- Department of Physiology, Providence College, Providence, RI, 02918, USA
| | - Hong-Duo Chen
- Department of Dermatology, No.1 Hospital of China Medical University, 155N. Nanjing Street, Shenyang, 110001, People's Republic of China.
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19
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Fiala O, Hosek P, Sorejs O, Liska V, Buchler T, Poprach A, Kucera R, Topolcan O, Sedivcova M, Finek J. The Association of Baseline Serum Tumour Markers with Outcome of Patients with Metastatic Colorectal Cancer Treated with Anti-EGFR Monoclonal Antibodies in the First Line. J Cancer 2018; 9:4255-4262. [PMID: 30519327 PMCID: PMC6277611 DOI: 10.7150/jca.26217] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2018] [Accepted: 07/22/2018] [Indexed: 12/13/2022] Open
Abstract
The measurement of serum tumour markers is a simple and non-invasive method for assessing the response to systemic therapies in metastatic colorectal cancer (mCRC) and estimation of prognosis. The aim of our retrospective study was to evaluate the association of baseline serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), thymidine kinase (TK) and tissue polypeptide specific antigen (TPS) with outcome of patients with mCRC treated with combination of chemotherapy and monoclonal antibodies against epidermal growth factor receptor (anti-EGFR mAbs) in the first line. In our study, the cohort included 102 patients treated with therapy based on anti-EGFR mAbs between years 2011 and 2017 at Department of Oncology and Radiotherapy, Medical School and University Hospital in Pilsen, Czech Republic. Serum samples were collected within one month before the initiation of treatment. In multivariate Cox analysis that included serum tumour markers and clinical baseline parameters show that high baseline serum CA 19-9 was significantly associated with worse progression-free survival (HR=1.871, p=0.0330) and also overall survival (HR=3.903, p=0.0006). We have not demonstrated association of baseline levels of CEA, TK and TPS with patients' outcome. CA 19-9 is commonly used serum tumour marker which is simple and readily available and its candidate prognostic importance in the setting of anti-EGFR therapy deserves to be studied in prospective trials.
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Affiliation(s)
- Ondrej Fiala
- Department of Oncology and Radiotherapy, Medical School and University Hospital in Pilsen, Charles University, Czech Republic.,Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Czech Republic
| | - Petr Hosek
- Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Czech Republic
| | - Ondrej Sorejs
- Department of Oncology and Radiotherapy, Medical School and University Hospital in Pilsen, Charles University, Czech Republic.,Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Czech Republic
| | - Vaclav Liska
- Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Czech Republic.,Department of Surgery, Medical School and University Hospital in Pilsen, Charles University, Czech Republic
| | - Tomas Buchler
- Department of Oncology and First Faculty of Medicine, Charles University and Thomayer Hospital, Czech Republic
| | - Alexandr Poprach
- Department of Comprehensive Cancer Care and Faculty of Medicine, Masaryk Memorial Cancer Institute and Masaryk University, Zluty kopec 543/7, 656 53 Brno, Czech Republic
| | - Radek Kucera
- Department of Immunochemistry, Medical School and University Hospital in Pilsen, Charles University, Czech Republic
| | - Ondrej Topolcan
- Department of Immunochemistry, Medical School and University Hospital in Pilsen, Charles University, Czech Republic
| | - Monika Sedivcova
- Bioptic Laboratory, Ltd., Molecular Pathology Laboratory, Pilsen, Czech Republic
| | - Jindrich Finek
- Department of Oncology and Radiotherapy, Medical School and University Hospital in Pilsen, Charles University, Czech Republic
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20
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Park J, Lee S, Kim Y, Choi A, Lee H, Lim J, Kim Y, Han K, Oh EJ. Comparison of Four Automated Carcinoembryonic Antigen Immunoassays: ADVIA Centaur XP, ARCHITECT I2000sr, Elecsys E170, and Unicel Dxi800. Ann Lab Med 2018; 38:355-361. [PMID: 29611386 PMCID: PMC5895865 DOI: 10.3343/alm.2018.38.4.355] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2017] [Revised: 11/01/2017] [Accepted: 02/20/2018] [Indexed: 12/05/2022] Open
Abstract
Background Carcinoembryonic antigen (CEA) is one of the tumor markers available for evaluating disease progression status after initial therapy and monitoring subsequent treatment modalities in colorectal, gastrointestinal, lung, and breast carcinoma. We evaluated the correlations and differences between widely used, automated CEA immunoassays at four different medical laboratories. Methods In total, 393 serum samples with CEA ranging from 3.0 to 1,000 ng/mL were analyzed on ADVIA Centaur XP (Siemens Diagnostics, Tarrytown, NY, USA), ARCHITECT i2000sr (Abbott Diagnostics, Abbott Park, IL, USA), Elecsys E170 (Roche Diagnostics, Indianapolis, IN, USA), and Unicel DxI800 (Beckman Coulter, Fullerton, CA, USA), and the results were compared. Deming regression, Passing-Bablok regression, and Bland-Altman analyses were performed to evaluate the data correlation and % differences among these assays. Results Deming regression analysis of data from Elecsys E170 and UniCel DxI800 showed good correlation (y=3.1615+0.8970x). According to Bland-Altman plot, no statistically significant bias (−1.78 ng/mL [95% confidence interval: −4.02 to 0.46]) was observed between Elecsys E170 and UniCel DxI800. However, the relative differences of CEA concentrations between assays exceeded the acceptable limit of 30%. Regarding the agreement of positivity with cut-off value 5.0 ng/mL, ARCHITECT i2000sr and Elecsys E170 showed the highest agreement (95.2%), whereas ADVIA Centaur XP and ARCHITECT i2000sr showed the lowest agreement (70.7%). Conclusions Agreements between automated CEA immunoassays are variable, and individual CEA concentrations may differ significantly between assays. Standardization of serum CEA concentrations and further harmonization are needed.
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Affiliation(s)
- Joonhong Park
- Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.,Catholic Laboratory Development and Evaluation Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Seungok Lee
- Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.,Catholic Laboratory Development and Evaluation Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yeongsic Kim
- Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.,Catholic Laboratory Development and Evaluation Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Aeran Choi
- Department of Laboratory Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea
| | - Hyeyoung Lee
- Department of Laboratory Medicine, Samkwang Medical Laboratories, Seoul, Korea
| | - Jihyang Lim
- Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.,Catholic Laboratory Development and Evaluation Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yonggoo Kim
- Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.,Catholic Laboratory Development and Evaluation Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Kyungja Han
- Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.,Catholic Laboratory Development and Evaluation Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Eun Jee Oh
- Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.,Catholic Laboratory Development and Evaluation Center, College of Medicine, The Catholic University of Korea, Seoul, Korea.
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21
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Saito G, Sadahiro S, Ogimi T, Miyakita H, Okada K, Tanaka A, Suzuki T. Relations of Changes in Serum Carcinoembryonic Antigen Levels before and after Neoadjuvant Chemoradiotherapy and after Surgery to Histologic Response and Outcomes in Patients with Locally Advanced Rectal Cancer. Oncology 2017; 94:167-175. [PMID: 29268274 DOI: 10.1159/000485511] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Accepted: 11/16/2017] [Indexed: 12/16/2022]
Abstract
OBJECTIVES The histologic response to neoadjuvant chemoradiotherapy (nCRT) has been intimately related to outcomes in locally advanced rectal cancer. Serum carcinoembryonic antigen (CEA) levels change after nCRT and after surgery as compared with before nCRT. METHODS The subjects were 149 patients with locally advanced rectal cancer who received nCRT between 2005 and 2013. The patients were divided into 4 groups according to the serum CEA levels: group 1, 55 patients with negative serum CEA levels before nCRT; group 2, 41 patients with positive serum CEA levels before nCRT that became negative after nCRT; group 3, 37 patients with positive serum CEA levels after nCRT that became negative after surgery; and group 4, 16 patients with positive serum CEA levels after nCRT as well as after surgery. RESULTS Pathological complete response, T downstaging, and tumor shrinkage were significantly higher in group 1 than in other groups. Disease-free survival was significantly poorer in group 4. The lack of a decrease in the serum CEA level in group 4 was most likely attributed to the persistence of micrometastases outside the resection field. CONCLUSIONS Changes in serum CEA levels measured before nCRT, after nCRT, and after surgery can be used to reliably predict the histologic response to nCRT and outcomes.
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Affiliation(s)
- Gota Saito
- Department of Surgery, Tokai University School of Medicine, Kanagawa, Japan
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22
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Pre-treatment carcinoembryonic antigen and outcome of patients with rectal cancer receiving neo-adjuvant chemo-radiation and surgical resection: a systematic review and meta-analysis. Med Oncol 2017; 34:177. [PMID: 28884291 DOI: 10.1007/s12032-017-1037-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Accepted: 09/05/2017] [Indexed: 12/22/2022]
Abstract
Neo-adjuvant chemo-radiation is the standard of care for patients with locally advanced rectal carcinoma. The aim of the present paper is to evaluate the relationship of the baseline serologic concentration of the carcinoembryonic antigen with the outcome. Data sources included MEDLINE and Web of Science databases. A systematic search of the databases by a predefined criterion has been conducted. Chemo-radiation followed by surgical resection of rectal tumors was the intervention of interest. From selected studies, the relationships between carcinoembryonic antigen and pathologic complete response, disease-free survival and overall survival were assessed. Carcinoembryonic antigen correlated significantly and inversely with the rate of pathologic complete responses (OR 2.00). Similar to this relationship, a low baseline carcinoembryonic antigen concentration was associated with a better disease-free survival (OR 1.88) and a better overall survival (OR 1.85). Heterogeneity of studies and publication bias were considerable in evaluating the relationship of baseline carcinoembryonic antigen and pathologic complete response. Baseline carcinoembryonic antigen should be regarded as a predictor of outcome of patients undergoing neo-adjuvant chemo-radiation. A calibration of the cutoff value from 5 to 3 ng/ml appears more appropriate to this patient population and should be evaluated in prospective trials.
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23
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Fan S, Li X, Zheng L, Hu D, Ren X, Ye Z. Correlations between the iodine concentrations from dual energy computed tomography and molecular markers Ki-67 and HIF-1α in rectal cancer: A preliminary study. Eur J Radiol 2017; 96:109-114. [PMID: 29103468 DOI: 10.1016/j.ejrad.2017.08.026] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2017] [Revised: 08/07/2017] [Accepted: 08/25/2017] [Indexed: 01/29/2023]
Abstract
PURPOSE To investigate whether dual energy computed tomography (CT) with iodine quantification is correlated with molecular markers Ki-67and hypoxia-inducible factor 1α (HIF-1α)in rectal cancer (RC). MATERIALS AND METHODS Eighty patients (43 males and 37 females) diagnosed with rectal cancer got pelvic contrast-enhanced CT scan with dual energy computed tomography before any anticancer treatment. Analyse the normalized iodine concentration (NIC) values and CT values at each energy level (40-140 keV) from the virtual monochromatic image of the primary lesions. The postoperative specimens of all 80 patients underwent Ki-67 and HIF-1α immunohistochemistry staining. By SPSS17.0 software package, we analyzed the correlations of NIC values and CT values at each energy level (40-140 keV) with Ki-67 and HIF-1α expression. The receiver operating characteristic (ROC) curves of these dual energy computed tomography parameters were calculated and the diagnostic value were assessed. RESULTS There was a weak positive correlation between NIC values and carcinoembryonic antigen level (r=0.246, P=0.028) in RC. Both the value and the level of Ki-67 expression were correlated positively with the NIC values (r=0.344, P=0.002 and r=0.248, P=0.026). HIF-1α expression was correlated positively with the NIC values of the RC (r=0.598, P<0.001). The best threshold values of NIC values in diagnosing the expression of HIF-1α was 0.5839. The sensitivity, 78%; specificity, 87%; PPV, 86%; NPV,79%;accuracy, 83%. CONCLUSION The NIC values on dual energy computed tomography may be used as a measurement of hypoxia in RC and determining the ability of tumor invasion noninvasively.
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Affiliation(s)
- Shuxuan Fan
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin 300060, China
| | - Xubin Li
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin 300060, China
| | - Lei Zheng
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin 300060, China
| | - Dongzhi Hu
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin 300060, China
| | - Xiaoyi Ren
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin 300060, China
| | - Zhaoxiang Ye
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin 300060, China.
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24
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Wilson MJ, van Haaren M, Harlaar JJ, Park HC, Bonjer HJ, Jeekel J, Zwaginga JJ, Schipperus M. Long-term prognostic value of preoperative anemia in patients with colorectal cancer: A systematic review and meta-analysis. Surg Oncol 2017; 26:96-104. [PMID: 28317592 DOI: 10.1016/j.suronc.2017.01.005] [Citation(s) in RCA: 59] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2016] [Revised: 01/12/2017] [Accepted: 01/31/2017] [Indexed: 12/12/2022]
Abstract
OBJECTIVE To evaluate the long-term prognostic factor of preoperative anemia in colorectal cancer patients. BACKGROUND Anemia is frequently observed in colorectal cancer patients, with a case incidence of 30 to 67 percent. Besides an indicator of tumor-induced blood loss and inflammation, anemia in cancer is also suggested to be a cause of inferior outcome, possibly via worsening of tumor hypoxia. As surgery is likely to enhance anemia, the long-term prognostic value of preoperative anemia seems most interesting. METHODS Comprehensive searches were carried out in all relevant databases, including MEDLINE, Embase and Web-of-Science. To include studies addressing overall survival, follow-up had to be at least 24 months or till death. For pooling of survival results, a mixed-linear (fixed-effects) model was fit to the reported hazard ratios (HRs) to calculate a pooled estimate and confidence interval. RESULTS We included 12 studies comprising 3588 patients to estimate the association between preoperative anemia and overall survival (OS) and disease-free survival (DFS). In a fixed-effects meta-analysis of eight studies, including both colon and rectal cancer, preoperative anemia was significantly associated with poor OS (HR 1.56; 95% CI 1.30 to 1.88; p < 0.001). A meta-analysis of seven studies also showed that preoperative anemia was significantly associated with poor DFS (HR 1.34; 95% CI 1.11 to 1.61; p = 0.002). Restricted to studies exclusively on colon cancer or rectal cancer, HRs for OS were 1.25 (95% CI 1.00 to 1.55; p = 0.05) and 2.59 (95% CI 1.68 to 4.01; p < 0.001), respectively, while HRs for DFS were 1.21 (95% CI 0.96 to 1.52; p = 0.11) and 1.61 (95% CI 1.18 to 2.21; p = 0.003). CONCLUSION The present meta-analysis reveals that preoperative anemia is significantly associated with decreased long-term OS and DFS in rectal cancer, but not in colon cancer patients, although this meta-analysis is mainly based on retrospective studies with high heterogeneity. These results justify raised awareness about the impact of preoperative anemia on long-term survival.
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Affiliation(s)
- M J Wilson
- TRIP Hemovigilance and Biovigilance Office, Leiden, The Netherlands; Erasmus University Medical Center Rotterdam, Department of Surgery, The Netherlands.
| | - M van Haaren
- OLVG Amsterdam, Department of Internal Medicine, The Netherlands
| | - J J Harlaar
- Westfriesgasthuis Hoorn, Department of Surgery, The Netherlands; VU Medical Center Amsterdam, Department of Surgery, The Netherlands
| | - Hee Chul Park
- Samsung Medical Center, Sungkyunkwan University School of Medicine, Department of Radiation Oncology, Seoul, South Korea
| | - H J Bonjer
- VU Medical Center Amsterdam, Department of Surgery, The Netherlands
| | - J Jeekel
- Erasmus University Medical Center Rotterdam, Department of Neuroscience, The Netherlands
| | - J J Zwaginga
- Center for Clinical Transfusion Research, Sanquin Research, Leiden, The Netherlands; Leiden University Medical Center, Department of Immunohematology and Blood Transfusion, The Netherlands
| | - M Schipperus
- Haga Ziekenhuis Den Haag, Department of Hematology, The Netherlands; TRIP Hemovigilance and Biovigilance Office, Leiden, The Netherlands
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Partial Oxygen Pressure Affects the Expression of Prognostic Biomarkers HIF-1 Alpha, Ki67, and CK20 in the Microenvironment of Colorectal Cancer Tissue. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2016; 2016:1204715. [PMID: 27974949 PMCID: PMC5126433 DOI: 10.1155/2016/1204715] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/05/2016] [Revised: 08/03/2016] [Accepted: 10/04/2016] [Indexed: 12/28/2022]
Abstract
Hypoxia is prognostically important in colorectal cancer (CRC) therapy. Partial oxygen pressure (pO2) is an important parameter of hypoxia. The correlation between pO2 levels and expression levels of prognostic biomarkers was measured in CRC tissues. Human CRC tissues were collected and pO2 levels were measured by OxyLite. Three methods for tissue fixation were compared, including formalin, Finefix, and Finefix-plus-microwave. Immunohistochemistry (IHC) staining was conducted by using the avidin-biotin complex technique for detecting the antibodies to hypoxia inducible factor-1 (HIF-1) alpha, cytokeratin 20 (CK20), and cell proliferation factor Ki67. The levels of pO2 were negatively associated with the size of CRC tissues. Finefix-plus-microwave fixation has the potential to replace formalin. Additionally, microwave treatment improved Finefix performance in tissue fixation and protein preservation. The percentage of positive cells and gray values of HIF-1 alpha, CK20, and Ki67 were associated with CRC development (P < 0.05). The levels of pO2 were positively related with the gray values of Ki67 and negatively related with the values of HIF-1 alpha and CK20 (P < 0.05). Thus, the levels of microenvironmental pO2 affect the expression of predictive biomarkers HIF-1 alpha, CK20, and Ki67 in the development of CRC tissues.
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The Association of Serum Carcinoembryonic Antigen, Carbohydrate Antigen 19-9, Thymidine Kinase, and Tissue Polypeptide Specific Antigen with Outcomes of Patients with Metastatic Colorectal Cancer Treated with Bevacizumab: a Retrospective Study. Target Oncol 2016; 10:549-55. [PMID: 25875421 DOI: 10.1007/s11523-015-0365-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The aim of our retrospective study was to analyze the association of selected tumor markers (TMs) including serum carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), thymidine kinase, and tissue polypeptide specific antigen with outcomes in patients with metastatic colorectal cancer (mCRC) treated with bevacizumab. There is an increasing body of evidence from retrospective/observational studies that some serum TMs may be predictive of effect of targeted therapies in mCRC. In our study, the cohort included 152 patients treated with bevacizumab-based therapy between years 2005 and 2014 at Department of Oncology and Radiotherapy, Medical School and Teaching Hospital Pilsen. Serum samples for measurement of TMs were collected within 1 month before the initiation of bevacizumab-based treatment. In multivariate Cox analysis that included serum tumor markers and clinical baseline parameters, the number of metastatic sites (hazard ratio [HR] = 2.00, p = 0.001) and CEA levels (HR = 2.80, p < 0.001) were significantly associated with progression-free survival, whereas CA 19-9 levels (HR = 2.25, p = 0.008) were the only studied parameter associated with overall survival. Quantification of serum CEA and CA 19-9 is simple and readily available, and their candidate prognostic importance in the setting of antiangiogenesis therapy deserves to be studied in prospective trials.
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Shi P, Zhong J, Hong J, Huang R, Wang K, Chen Y. Automated Ki-67 Quantification of Immunohistochemical Staining Image of Human Nasopharyngeal Carcinoma Xenografts. Sci Rep 2016; 6:32127. [PMID: 27562647 PMCID: PMC4999801 DOI: 10.1038/srep32127] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2016] [Accepted: 08/02/2016] [Indexed: 01/15/2023] Open
Abstract
Nasopharyngeal carcinoma is one of the malignant neoplasm with high incidence in China and south-east Asia. Ki-67 protein is strictly associated with cell proliferation and malignant degree. Cells with higher Ki-67 expression are always sensitive to chemotherapy and radiotherapy, the assessment of which is beneficial to NPC treatment. It is still challenging to automatically analyze immunohistochemical Ki-67 staining nasopharyngeal carcinoma images due to the uneven color distributions in different cell types. In order to solve the problem, an automated image processing pipeline based on clustering of local correlation features is proposed in this paper. Unlike traditional morphology-based methods, our algorithm segments cells by classifying image pixels on the basis of local pixel correlations from particularly selected color spaces, then characterizes cells with a set of grading criteria for the reference of pathological analysis. Experimental results showed high accuracy and robustness in nucleus segmentation despite image data variance. Quantitative indicators obtained in this essay provide a reliable evidence for the analysis of Ki-67 staining nasopharyngeal carcinoma microscopic images, which would be helpful in relevant histopathological researches.
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Affiliation(s)
- Peng Shi
- School of Mathematics and Computer Science, Fujian Normal University, Fuzhou, Fujian 350117, China
| | - Jing Zhong
- The Graduate School, Fujian Medical University, Fuzhou, Fujian 350004, China
| | - Jinsheng Hong
- Department of Radiation Oncology, Laboratory of Radiation Biology, First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350005, China
| | - Rongfang Huang
- Department of Pathology, Fujian Provincial Cancer Hospital, Fuzhou, Fujian 350014, China
| | - Kaijun Wang
- School of Mathematics and Computer Science, Fujian Normal University, Fuzhou, Fujian 350117, China
| | - Yunbin Chen
- The Graduate School, Fujian Medical University, Fuzhou, Fujian 350004, China.,Department of Radiology, Fujian Provincial Cancer Hospital, Fuzhou, Fujian 350014, China
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Abe S, Kawai K, Ishihara S, Nozawa H, Hata K, Kiyomatsu T, Tanaka T, Watanabe T. Prognostic impact of carcinoembryonic antigen and carbohydrate antigen 19-9 in stage IV colorectal cancer patients after R0 resection. J Surg Res 2016; 205:384-392. [PMID: 27664887 DOI: 10.1016/j.jss.2016.06.078] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Revised: 06/08/2016] [Accepted: 06/27/2016] [Indexed: 01/04/2023]
Abstract
BACKGROUND Although preoperative carcinoembryonic antigen (pre-CEA) and carbohydrate antigen 19-9 (pre-CA 19-9) are reportedly prognostic indicators for colorectal cancer (CRC), the prognostic roles of postoperative CEA (post-CEA) and CA 19-9 (post-CA 19-9) shortly after surgery have not been clarified in patients with curatively resected stage IV CRC. The aim of this study was to evaluate the predictive abilities of post-CEA and post-CA 19-9. METHODS A total of 129 consecutive patients who had stage IV CRC and underwent R0 resection were retrospectively analyzed. Pre-CEA and post-CEA and CA 19-9 levels were measured within 1 mo before and 3 mo after surgery, respectively. Relapse-free survival (RFS) and overall survival were estimated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazards model. RESULTS Pre-CEA was elevated (≥5.0 ng/mL) in 73.6% of the patients and remained elevated after surgery in 32.7% of the patients. Elevated post-CA 19-9 (≥50 U/mL) was observed in 9.5% of the patients. Neither elevated pre-CEA nor elevated pre-CA 19-9 was significantly associated with RFS but both elevated post-CEA and elevated post-CA 19-9 were associated with markedly reduced RFS (P = 0.0002 and P = 0.0004, respectively). When considered in combination, post-CEA and post-CA 19-9 significantly stratified RFS and was an independent predictive factor for recurrence (P = 0.0035), as was lymphatic invasion (P = 0.0015). Post-CA 19-9 was the only evident independent predictive factor for overall survival (P = 0.0336). CONCLUSIONS In patients with stage IV CRC who underwent curative resection, the combination of post-CEA and post-CA 19-9 at 3 mo after surgery was a potent prognostic indicator for recurrence.
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Affiliation(s)
- Shinya Abe
- Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
| | - Kazushige Kawai
- Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Soichiro Ishihara
- Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroaki Nozawa
- Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Keisuke Hata
- Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tomomichi Kiyomatsu
- Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Toshiaki Tanaka
- Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Toshiaki Watanabe
- Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
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Wuxiao ZJ, Zhou HY, Wang KF, Chen XQ, Hao XB, Lu YD, Xia ZJ. A prognostic model to predict survival in stage III colon cancer patients based on histological grade, preoperative carcinoembryonic antigen level and the neutrophil lymphocyte ratio. Asian Pac J Cancer Prev 2015; 16:747-51. [PMID: 25684519 DOI: 10.7314/apjcp.2015.16.2.747] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Stage III colon cancer patients demonstrate diverse clinical outcomes. The aim of this study was to develop a prognostic model in order to better predict their survival. MATERIALS AND METHODS From 2004 to 2010, 548 patients were retrospectively analyzed, among whom 328 were defined as the study group and the remaining 220 served as a validation group. Clinico-pathologic features, including age, gender, histological grade, T stage, number of positive lymph nodes, number of harvest lymph nodes, pretreatment carcinoembryonic antigen (CEA) levels and pretreatment neutrophil lymphocyte ratio (NLR), were collected. Kaplan-Meier survival curves were used to detect prognostic factors and multivariate analysis was applied to identify independent examples on which to develop a prognostic model. Finally, the model was further validated with the validation group. RESULTS Histological grade (p=0.002), T stage (p=0.011), number of positive lymph nodes (p=0.003), number of harvested lymph nodes (p=0.020), CEA (p=0.005), and NLR (p<0.001) were found as prognostic factors while histological grade [RR(relative risk):0.632, 95%CI (Confidence interval) 0.405~0.985, p=0.043], CEA (RR:0.644, 95%CI:0.431~0.964, p=0.033) and NLR (RR:0.384, 95%CI:0.255~0.580, p<0.001) levels were independent. The prognostic model based on these three factors was able to classify patients into high risk, intermediate and low risk groups (p<0.001), both in study and validation groups. CONCLUSIONS Histological grade, pretreatment CEA and NLR levels are independent prognostic factors in stage III colon cancer patients. A prognostic model based on these factors merits attention in future clinical practice.
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Affiliation(s)
- Zhi-Jun Wuxiao
- Department of Hematology and Oncology, the Affiliated Hospital of Hainan Medical College, Haikou, Hainan, P.R. China E-mail :
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Piri R, Ghaffari A, Gholami N, Azami-Aghdash S, PourAli-Akbar Y, Saleh P, Naghavi-Behzad M. Ki-67/MIB-1 as a Prognostic Marker in Cervical Cancer - a Systematic Review with Meta-Analysis. Asian Pac J Cancer Prev 2015; 16:6997-7002. [DOI: 10.7314/apjcp.2015.16.16.6997] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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Borda A, Prieto C, Jiménez J, Vila J, Zozaya JM, Borda F. [Prognostic value of preoperative carcinoembryogenic antigen: Is it useful in all stages of colorectal cancer?]. GASTROENTEROLOGIA Y HEPATOLOGIA 2015; 39:191-8. [PMID: 26117267 DOI: 10.1016/j.gastrohep.2015.05.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/27/2015] [Revised: 05/05/2015] [Accepted: 05/06/2015] [Indexed: 01/07/2023]
Abstract
INTRODUCTION Recent reports have reopened discussion of the prognostic value of elevated pre-treatment carcinoembryonic antigen (CEA) levels in colorectal cancer. Due to the discrepancies in the published results, we aimed to analyze the possible predictive value of CEA, both overall and in different tumoral stages in our environment. PATIENTS AND METHODS We retrospectively studied 303 consecutive patients with colorectal cancer resected with curative intent by analysing tumor-related mortality. The frequency of patients with increased CEA levels (> 5mg/l) was registered. Univariate and multivariate analyses of survival curves were performed, comparing patients with increased CEA levels and those with CEA levels within normal limits, both in the overall series and in the different pTNM tumoral stages. RESULTS Frequency of patients with CEA>5mg/l was 31%. The median clinical follow-up was 83 months. A poor survival rate was registered in the multivariate analysis of the whole series in patients with high CEA levels: hazard ratio (HR)=1.81; 95% confidence interval (95% CI)=(1.15-3.10); P=.012. This predictive value was only maintained in stage II in the survival analysis of the distinct tumoral stages (n=104): HR=3.02; 95% CI=(1.22-7.45); P=.017. CONCLUSIONS Before treatment, 31% of our patients with colorectal cancer resected with curative intent had pathological CEA values. In the overall series, a high pretreatment CEA level showed an independent prognostic value for poor survival. When pTNM tumoral stages were analyzed separately, CEA level had predictive value only in pTNM II tumors.
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Affiliation(s)
- Ana Borda
- Servicio de Digestivo, Complejo Hospitalario de Navarra, Instituto de Investigaciones Sanitarias de Navarra (IDISNA), Pamplona, España.
| | - Carlos Prieto
- Servicio de Digestivo, Complejo Hospitalario de Navarra, Instituto de Investigaciones Sanitarias de Navarra (IDISNA), Pamplona, España
| | - Javier Jiménez
- Servicio de Digestivo, Complejo Hospitalario de Navarra, Instituto de Investigaciones Sanitarias de Navarra (IDISNA), Pamplona, España
| | - Juan Vila
- Servicio de Digestivo, Complejo Hospitalario de Navarra, Instituto de Investigaciones Sanitarias de Navarra (IDISNA), Pamplona, España
| | - José Manuel Zozaya
- Servicio de Digestivo, Complejo Hospitalario de Navarra, Instituto de Investigaciones Sanitarias de Navarra (IDISNA), Pamplona, España
| | - Fernando Borda
- Servicio de Digestivo, Complejo Hospitalario de Navarra, Instituto de Investigaciones Sanitarias de Navarra (IDISNA), Pamplona, España
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Serine Protease Inhibitor Kazal Type 1 (SPINK1) Promotes Proliferation of Colorectal Cancer Through the Epidermal Growth Factor as a Prognostic Marker. Pathol Oncol Res 2015; 21:1201-8. [PMID: 26037168 DOI: 10.1007/s12253-015-9949-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2014] [Accepted: 05/08/2015] [Indexed: 10/23/2022]
Abstract
Serine protease inhibitor Kazal type-1 (SPINK1), a trypsin kinase inhibitor, is involved in inflammation, cell proliferation and carcinogenesis. The role and association between SPINK1, EGFR and Ki-67 in colorectal adenoma (CRA) and colorectal cancer (CRC) are still unknown. In this study, we used immunohistochemical stain to evaluate expression of SPINK1, EGFR and Ki-67 proteins in 30 CRA and 53 CRC patients semiquantitatively, and then analyzed their correlation with clinicopathologic parameters. Our results revealed that SPINK1 expression was noted in the upper and basal parts of the crypts in CRA and was more intensely related with cellular atypia. EGFR expression was found in 13 out of 30 adenomas, including 9 out of 15 adenomas with dysplasia or synchronous CRC (60 %), and 4 out of 15 adenomas without dysplasia (26.7 %). In CRC, high SPINK1 expression was significantly associated with males (p = 0.041) and advanced disease stage (p = 0.015). EGFR positivity was significantly correlated with higher T stage (p = 0.004) and disease stage (stage I-IV, p = 0.017; early vs. late, p = 0.015). Pearson's correlation showed positive correlation between the SPINK1 intensity and EGFR immunoreactivity (p = 0.011), and Ki-67 and SPINK1 intensity or percentage (p = 0.017 and p = 0.039 respectively). In Kaplan-Meier analyses, patients with high SPINK1 intensity tended to have shorter overall survival (p = 0.03). Concomitant expression of high SPINK1 intensity and EGFR was also identified as being associated with poor prognosis (p = 0.015). In conclusion, high SPINK1 expression is associated with advanced stage and poor prognosis. There is positive correlation between high SPINK1 expression, EGFR immunoreactivity, and high Ki-67 labeling index. The SPINK1 protein seems to play a role in tumor proliferation and malignant transformation through the EGFR pathway. SPINK1 may serve as a prognostic biomarker in therapeutic targeting in the future.
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Thammasit P, Sangboonruang S, Suwanpairoj S, Khamaikawin W, Intasai N, Kasinrerk W, Tayapiwatana C, Tragoolpua K. Intracellular Acidosis Promotes Mitochondrial Apoptosis Pathway: Role of EMMPRIN Down-regulation via Specific Single-chain Fv Intrabody. J Cancer 2015; 6:276-86. [PMID: 25663946 PMCID: PMC4317764 DOI: 10.7150/jca.10879] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2014] [Accepted: 12/31/2014] [Indexed: 02/06/2023] Open
Abstract
Extracellular matrix metalloproteinase inducer (EMMPRIN) is a human leukocyte surface molecule that is enriched on the surface of many cancer cells, and it plays an important role in proliferation and metastasis. In this study, we utilized the chimeric adenoviral vector Ad5/F35 carrying gene encoding scFv against EMMPRIN (scFv-M6-1B9) to down-regulate EMMPRIN cell surface expression and investigated programmed cell death response in colorectal cancer (CRC) cell, Caco-2. The scFv-M6-1B9 intrabody exhibits robust activity in reducing EMMPRIN cell surface expression. This approach led to the inducing of apoptosis, which was relative to the increasing of apoptotic bodies in sub-G1 peak, phosphatidylserine externalization, as well as TUNEL-positive cells. In addition, real-time RT-PCR and western blotting analysis indicated that apoptosis was enhanced through the mitochondrial pathway, a marked reduction of Bcl-2, leading to the translocation of cytochrome c and also the dramatic activation of caspase-3. Moreover, carcinoembryonic antigen (CEA), a tumor marker for CRC, was found to have significantly diminished in both secreted protein and mRNA levels. In conclusion, these findings suggest that EMMPRIN down-regulation by scFv-M6-1B9 intrabody has great potential in enhancing the efficacy of apoptosis induction through the mitochondrial pathway and in effecting a decline in the CEA level. Thus, its benefits could be applied to project the future prospects for targeted gene therapy and therapeutic application in monitoring colorectal cancer.
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Affiliation(s)
- Patcharin Thammasit
- 1. Division of Clinical Microbiology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand
| | - Sirikwan Sangboonruang
- 1. Division of Clinical Microbiology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand
| | - Supattara Suwanpairoj
- 2. Division of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand
| | - Wannisa Khamaikawin
- 2. Division of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand
| | - Nutjeera Intasai
- 3. Division of Clinical Microscopy, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand
| | - Watchara Kasinrerk
- 2. Division of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand ; 4. Biomedical Technology Research Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency at the Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand
| | - Chatchai Tayapiwatana
- 2. Division of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand ; 4. Biomedical Technology Research Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency at the Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand ; 5. BioMedical Engineering Center, Chiang Mai University, Chiang Mai, Thailand
| | - Khajornsak Tragoolpua
- 1. Division of Clinical Microbiology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand
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Oliver JA, Ortiz R, Melguizo C, Álvarez PJ, Gómez-Millán J, Prados J. Prognostic impact of MGMT promoter methylation and MGMT and CD133 expression in colorectal adenocarcinoma. BMC Cancer 2014; 14:511. [PMID: 25015560 PMCID: PMC4227111 DOI: 10.1186/1471-2407-14-511] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2014] [Accepted: 07/07/2014] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND New biomarkers are needed for the prognosis of advanced colorectal cancer, which remains incurable by conventional treatments. O6-methylguanine DNA methyltransferase (MGMT) methylation and protein expression have been related to colorectal cancer treatment failure and tumor progression. Moreover, the presence in these tumors of cancer stem cells, which are characterized by CD133 expression, has been associated with chemoresistance, radioresistance, metastasis, and local recurrence. The objective of this study was to determine the prognostic value of CD133 and MGMT and their possible interaction in colorectal cancer patients. METHODS MGMT and CD133 expression was analyzed by immunohistochemistry in 123 paraffin-embedded colorectal adenocarcinoma samples, obtaining the percentage staining and intensity. MGMT promoter methylation status was obtained by using bisulfite modification and methylation-specific PCR (MSP). These values were correlated with clinical data, including overall survival (OS), disease-free survival (DFS), tumor stage, and differentiation grade. RESULTS Low MGMT expression intensity was significantly correlated with shorter OS and was a prognostic factor independently of treatment and histopathological variables. High percentage of CD133 expression was significantly correlated with shorter DFS but was not an independent factor. Patients with low-intensity MGMT expression and ≥50% CD133 expression had the poorest DFS and OS outcomes. CONCLUSIONS Our results support the hypothesis that MGMT expression may be an OS biomarker as useful as tumor stage or differentiation grade and that CD133 expression may be a predictive biomarker of DFS. Thus, MGMT and CD133 may both be useful for determining the prognosis of colorectal cancer patients and to identify those requiring more aggressive adjuvant therapies. Future studies will be necessary to determine its clinical utility.
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Affiliation(s)
- Jaime Antonio Oliver
- Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, Granada 18100, Spain
| | - Raúl Ortiz
- Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, Granada 18100, Spain
- Department of Health Sciences, University of Jaén, Jaén 23071, Spain
- Biosanitary Institute of Granada (ibs.GRANADA), SAS-Universidad de Granada, Granada, Spain
| | - Consolación Melguizo
- Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, Granada 18100, Spain
- Biosanitary Institute of Granada (ibs.GRANADA), SAS-Universidad de Granada, Granada, Spain
- Department of Anatomy and Embryology, University of Granada, Granada 18012, Spain
| | - Pablo Juan Álvarez
- Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, Granada 18100, Spain
- Biosanitary Institute of Granada (ibs.GRANADA), SAS-Universidad de Granada, Granada, Spain
| | - Jaime Gómez-Millán
- Radiation Oncology Department, Hospital Clinico Universitario Virgen de la Victoria, Málaga 29010, Spain
| | - Jose Prados
- Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, Granada 18100, Spain
- Biosanitary Institute of Granada (ibs.GRANADA), SAS-Universidad de Granada, Granada, Spain
- Department of Anatomy and Embryology, University of Granada, Granada 18012, Spain
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Duffy MJ, Lamerz R, Haglund C, Nicolini A, Kalousová M, Holubec L, Sturgeon C. Tumor markers in colorectal cancer, gastric cancer and gastrointestinal stromal cancers: European group on tumor markers 2014 guidelines update. Int J Cancer 2014; 134:2513-22. [PMID: 23852704 PMCID: PMC4217376 DOI: 10.1002/ijc.28384] [Citation(s) in RCA: 245] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2013] [Accepted: 06/25/2013] [Indexed: 02/06/2023]
Abstract
Biomarkers currently play an important role in the detection and management of patients with several different types of gastrointestinal cancer, especially colorectal, gastric, gastro-oesophageal junction (GOJ) adenocarcinomas and gastrointestinal stromal tumors (GISTs). The aim of this article is to provide updated and evidence-based guidelines for the use of biomarkers in the different gastrointestinal malignancies. Recommended biomarkers for colorectal cancer include an immunochemical-based fecal occult blood test in screening asymptomatic subjects ≥50 years of age for neoplasia, serial CEA levels in postoperative surveillance of stage II and III patients who may be candidates for surgical resection or systemic therapy in the event of distant metastasis occurring, K-RAS mutation status for identifying patients with advanced disease likely to benefit from anti-EGFR therapeutic antibodies and microsatellite instability testing as a first-line screen for subjects with Lynch syndrome. In advanced gastric or GOJ cancers, measurement of HER2 is recommended in selecting patients for treatment with trastuzumab. For patients with suspected GIST, determination of KIT protein should be used as a diagnostic aid, while KIT mutational analysis may be used for treatment planning in patients with diagnosed GISTs.
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Affiliation(s)
- MJ Duffy
- Clinical Research Center, St Vincent’s University Hospital, Dublin 4 and UCD School of Medicine and Medical Science, Conway Institute, University College DublinDublin, Ireland
| | - R Lamerz
- Medical Department II, Klinikum Grosshadern, Med. Klinik IIMunich, Germany
| | - C Haglund
- Department of Surgery, Helsinki University Central HospitalHelsinki, Finland
| | - A Nicolini
- Department of Oncology, University of PisaPisa, Italy
| | - M Kalousová
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University in Prague and General University Hospital in PraguePrague, Czech Republic
| | - L Holubec
- Department of Oncology and Radiotherapy, University Hospital of PilsenPilsen, Czech Republic
| | - C Sturgeon
- Department of Clinical Biochemistry, Royal Infirmary of EdinburghEdinburgh, United Kingdom
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Zhang BX, Pan HD, Gao ZY, Gu J, Zhao J. Multivariate analysis of prognostic factors for patients with colon carcinoma. Shijie Huaren Xiaohua Zazhi 2014; 22:2202-2207. [DOI: 10.11569/wcjd.v22.i15.2202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the prognostic factors for colon carcinoma by analyzing its clinical and pathological characteristics.
METHODS: We retrospectively reviewed the demographic, clinical, histopathological, and laboratory data for consecutive patients with colon cancer who underwent curative surgery alone from July 2007 to May 2010 at Peking University Cancer Hospital. Unvaried and multivariate analyses were conducted to identify prognostic factors for colon carcinoma.
RESULTS: A total of 226 valid cases were reviewed in this study, and their 3-year overall survival rate was 81.9%. Univariate analysis showed that preoperative CEA level > 5 ng/mL, poor differentiation, age < 40, blood transfusion, higher T stage, higher N stage, metastasis and lymphatic vessel invasion were poor prognostic factors for patients with colon cancer (P < 0.05). Multivariate analysis found that preoperative CEA level (P = 0.017), higher N stage (P = 0.005), poor differentiation (P = 0.002), and higher M stage (P = 0.000) were the independent prognostic factors for colon carcinoma.
CONCLUSION: Based on the prognostic risk factors such as preoperative CEA level, poor differentiation, higher N stage and metastasis, more accurate risk stratification can be conducted in patients with colon cancer. Patients with such risk factors should be considered as candidates for receiving more intensive treatment and surveillance.
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Lin L, Piao J, Gao W, Piao Y, Jin G, Ma Y, Li J, Lin Z. DEK over expression as an independent biomarker for poor prognosis in colorectal cancer. BMC Cancer 2013; 13:366. [PMID: 23902796 PMCID: PMC3751154 DOI: 10.1186/1471-2407-13-366] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2013] [Accepted: 06/28/2013] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND The DEK protein is related to chromatin reconstruction and gene transcription, and plays an important role in cell apoptosis. High expression levels of the human DEK gene have been correlated with numerous human malignancies. This study explores the roles of DEK in tumor progression and as a prognostic determinant of colorectal cancer. METHODS Colorectal cancer specimens from 109 patients with strict follow-up, and colorectal adenomas from 52 patients were selected for analysis of DEK protein by immunohistochemistry. The correlations between DEK over expression and the clinicopathological features of colorectal cancers were evaluated by Chi-square test and Fisher's exact tests. The survival rates were calculated by the Kaplan-Meier method, and the relationship between prognostic factors and patient survival was also analyzed by the Cox proportional hazard models. RESULTS DEK protein showed a nuclear immunohistochemical staining pattern in colorectal cancers. The strongly positive rate of DEK protein was 48.62% (53/109) in colorectal cancers, which was significantly higher than that in either adjacent normal colon mucosa (9.17%, 10/109) or colorectal adenomas (13.46%, 7/52). DEK over expression in colorectal cancers was positively correlated with tumor size, grade, lymph node metastasis, serosal invasion, late stage, and disease-free survival- and 5-year survival rates. Further analysis showed that patients with late stage colorectal cancer and high DEK expression had worse survival rates than those with low DEK expression. Moreover, multivariate analysis showed high DEK expression, serosal invasion, and late stage are significant independent risk factors for mortality in colorectal cancer. CONCLUSIONS DEK plays an important role in the progression of colorectal cancers and it is an independent poor prognostic factor of colorectal cancers.
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Affiliation(s)
- Lijuan Lin
- Department of Pathology, Yanbian University College of Medicine, Yanji 133002, China
- Department of Medical Imaging, Eastern Liaoning University College of Medicine, Dandong 118002, China
| | - Junjie Piao
- Department of Pathology, Yanbian University College of Medicine, Yanji 133002, China
| | - Wenbin Gao
- Department of Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian 116000, China
| | - Yingshi Piao
- Cancer Research Center, Yanbian University, Yanji 133002, China
| | - Guang Jin
- Cancer Research Center, Yanbian University, Yanji 133002, China
| | - Yue Ma
- Department of Pathology, Yanbian University College of Medicine, Yanji 133002, China
| | - Jinzi Li
- Department of Pathology, Yanbian University College of Medicine, Yanji 133002, China
- Department of Internal Medicine, Yanbian University Affiliated Hospital, Yanji 133000, China
| | - Zhenhua Lin
- Department of Pathology, Yanbian University College of Medicine, Yanji 133002, China
- Cancer Research Center, Yanbian University, Yanji 133002, China
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Combined preoperative CEA and CD44v6 improves prognostic value in patients with stage I and stage II colorectal cancer. Clin Transl Oncol 2013; 16:285-92. [PMID: 23860725 DOI: 10.1007/s12094-013-1069-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2013] [Accepted: 06/16/2013] [Indexed: 12/15/2022]
Abstract
AIM Combination of biomarkers may improve diagnosis and have better prognostic value than single markers. The purpose of this study was to investigate whether combined CEA and CD44v6 improves prognostic value in stage I and stage II (stage I/II) colorectal cancer (CRC). METHODS Preoperative serum CEA level and the expression of CD44v6 in CRC tissues were examined by electrochemiluminescence immunoassay and immunohistochemistry, respectively. The association of CEA and CD44v6 with clinicopathological features and their possible prognostic values was analyzed. RESULTS The preoperative elevated serum CEA level and positive CD44v6 expression were detected in 30.1 % (52/173) serum samples and 60.5 % (101/167) CRC tissues, respectively. Patients with an elevated-CEA level or a CD44v6-negative tumor had a worse disease-specific survival (DSS) than those with a normal-CEA level or CD44v6-positive tumor (P = 0.024, P = 0.012, respectively). Moreover, CD44v6 expression could be used in discriminating patients from good to poor prognosis in normal-CEA subgroup (P = 0.043), but not in elevated-CEA subgroup (P = 0.563). Multivariate analysis revealed that combined CEA and CD44v6 was an independent prognostic factor for patients with stage I/II CRC (P = 0.023). However, serum CEA level only retained a borderline significance for correlation with a worse DSS (P = 0.059), and CD44v6 expression alone was not an independent prognostic factor for DSS in multivariate analysis (P = 0.123). CONCLUSION These results suggested that combined CEA/CD44v6 had better prognostic value than CEA or CD44v6 alone for patients with stage I/II CRC.
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