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1
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Peng H, Pan M, Zhou Z, Chen C, Xing X, Cheng S, Zhang S, Zheng H, Qian K. The impact of preanalytical variables on the analysis of cell-free DNA from blood and urine samples. Front Cell Dev Biol 2024; 12:1385041. [PMID: 38784382 PMCID: PMC11111958 DOI: 10.3389/fcell.2024.1385041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2024] [Accepted: 04/22/2024] [Indexed: 05/25/2024] Open
Abstract
Cell-free DNA (cfDNA), a burgeoning class of molecular biomarkers, has been extensively studied across a variety of biomedical fields. As a key component of liquid biopsy, cfDNA testing is gaining prominence in disease detection and management due to the convenience of sample collection and the abundant wealth of genetic information it provides. However, the broader clinical application of cfDNA is currently impeded by a lack of standardization in the preanalytical procedures for cfDNA analysis. A number of fundamental challenges, including the selection of appropriate preanalytical procedures, prevention of short cfDNA fragment loss, and the validation of various cfDNA measurement methods, remain unaddressed. These existing hurdles lead to difficulties in comparing results and ensuring repeatability, thereby undermining the reliability of cfDNA analysis in clinical settings. This review discusses the crucial preanalytical factors that influence cfDNA analysis outcomes, including sample collection, transportation, temporary storage, processing, extraction, quality control, and long-term storage. The review provides clarification on achievable consensus and offers an analysis of the current issues with the goal of standardizing preanalytical procedures for cfDNA analysis.
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Affiliation(s)
- Hongwei Peng
- Department of Biological Repositories, Human Genetic Resources Preservation Center of Hubei Province, Hubei Key Laboratory of Urological Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Ming Pan
- Taihe Skills Training Center, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China
| | - Zongning Zhou
- Department of Biological Repositories, Human Genetic Resources Preservation Center of Hubei Province, Hubei Key Laboratory of Urological Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Congbo Chen
- Department of Urology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China
| | - Xing Xing
- Department of Urology, The First Affiliated Hospital of Yangtze University, Jingzhou, Hubei, China
| | - Shaoping Cheng
- Department of Urology, The First Affiliated Hospital of Yangtze University, Jingzhou, Hubei, China
| | - Shanshan Zhang
- Department of Biological Repositories, Human Genetic Resources Preservation Center of Hubei Province, Hubei Key Laboratory of Urological Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Hang Zheng
- Department of Urology, Laboratory of Precision Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Kaiyu Qian
- Department of Biological Repositories, Human Genetic Resources Preservation Center of Hubei Province, Hubei Key Laboratory of Urological Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China
- Department of Urology, Laboratory of Precision Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China
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2
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Aquino IMC, Pascut D. Liquid biopsy: New opportunities for precision medicine in hepatocellular carcinoma care. Ann Hepatol 2024; 29:101176. [PMID: 37972709 DOI: 10.1016/j.aohep.2023.101176] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Accepted: 10/18/2023] [Indexed: 11/19/2023]
Abstract
Liquid biopsy, specifically the analysis of circulating tumor DNA (ctDNA), offers a non-invasive approach for hepatocellular carcinoma (HCC) diagnosis and management. However, its implementation in the clinical setting is difficult due to challenges such as low ctDNA yield and difficulty in understanding the mutation signals from background noise. This review highlights the crucial role of artificial intelligence (AI) in addressing these limitations and in improving discoveries in the field of liquid biopsy for HCC care. Combining AI with liquid biopsy data can offer a promising future for the discovery of novel biomarkers and an AI-powered clinical decision support system (CDSS) can turn liquid biopsy into an important tool for personalized management of HCC. Despite the current challenges, the integration of AI shows promise to significantly improve patient outcomes and revolutionize the field of oncology.
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Affiliation(s)
- Inah Marie C Aquino
- College of Medicine, University of the Philippines Manila, Ermita, Manila, Metro Manila 1000, Philippines; Liver Cancer Unit, Fondazione Italiana Fegato - ONLUS, Basovizza, Trieste 34149, Italy
| | - Devis Pascut
- Liver Cancer Unit, Fondazione Italiana Fegato - ONLUS, Basovizza, Trieste 34149, Italy.
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3
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Mohamed YI, Lee SS, Demir T, Chamseddine S, Hu ZI, Xiao L, Elsayes K, Morris JS, Wolff RA, Hiatia R, Qayyum A, Rashid A, Duda DG, Yao JC, LaPelusa M, Koay EJ, Mahvash A, Al Azzam A, Dumbrava EE, Hassan M, Amin HM, Kaseb AO. Circulating tumor DNA (ctDNA) as a biomarker of response to therapy in advanced Hepatocellular carcinoma treated with Nivolumab. Cancer Biomark 2024; 41:83-91. [PMID: 39269823 PMCID: PMC11491993 DOI: 10.3233/cbm-230431] [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] [Received: 09/28/2023] [Accepted: 08/18/2024] [Indexed: 09/15/2024]
Abstract
BACKGROUND Circulating tumor DNA (ctDNA) is a promising non-invasive marker for detection, diagnosis, treatment selection, and prognosis of hepatocellular carcinoma (HCC). OBJECTIVE This study aimed to examine the utility of ctDNA as a prognostic and predictive tool in HCC patients treated with nivolumab. METHODS We analyzed pre-treatment ctDNA from 44 HCC patients using comprehensive genomic testing on a commercially available platform. We utilized log rank test and univariate Cox models to correlate overall survival (OS) and progression-free survival (PFS) with ctDNA expressions. RESULTS Of 44 patients, 77.3% were men with median age of 67 years. All but 3 patients had at least one alteration identified, and TP53 was the most commonly altered gene (52.3%). Median OS was 17.5 months (95% CI: 12.7, NA). Mutations involving PIK3CA, BRCA1, and CCND1 amplification were associated with shorter OS (P 0.0001, 0.0001 and 0.01, respectively). Median PFS time was 4.01 months (95% CI: 3.06, 9.33). Mutations involving KIT and PIK3CA were associated with shorter PFS (P 0.0001 and 0.0004, respectively), while mutation involving CTNNB1 were associated with longer PFS (p= 0.04). CONCLUSIONS ctDNA profiling may provide a benefit for prediction of survival and progression of HCC patients treated with nivolumab. Future studies are needed for confirmation.
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Affiliation(s)
- Yehia I. Mohamed
- Department of Gastrointestinal Medical Oncology, M.D. Anderson Cancer Center, The University of Texas, Houston, TX, USA
| | - Sunyoung S. Lee
- Department of Gastrointestinal Medical Oncology, M.D. Anderson Cancer Center, The University of Texas, Houston, TX, USA
| | - Tarik Demir
- Department of Gastrointestinal Medical Oncology, M.D. Anderson Cancer Center, The University of Texas, Houston, TX, USA
| | - Shadi Chamseddine
- Department of Gastrointestinal Medical Oncology, M.D. Anderson Cancer Center, The University of Texas, Houston, TX, USA
| | - Zishuo Ian Hu
- Department of Gastrointestinal Medical Oncology, M.D. Anderson Cancer Center, The University of Texas, Houston, TX, USA
| | - Lianchun Xiao
- Department of Biostatistics, M.D. Anderson Cancer Center, The University of Texas, Houston, TX, USA
| | - Khaled Elsayes
- Department of Diagnostic Imaging, M.D. Anderson Cancer Center, The University of Texas, Houston, TX, USA
| | - Jeffrey S. Morris
- Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, PA, USA
| | - Robert A. Wolff
- Department of Gastrointestinal Medical Oncology, M.D. Anderson Cancer Center, The University of Texas, Houston, TX, USA
| | - Rikita Hiatia
- Department of Epidemiology, M.D. Anderson Cancer Center, The University of Texas, Houston, TX, USA
| | - Aliya Qayyum
- Department of Diagnostic Imaging, M.D. Anderson Cancer Center, The University of Texas, Houston, TX, USA
| | - Asif Rashid
- Department of Pathology, M.D. Anderson Cancer Center, The University of Texas, Houston, TX, USA
| | - Dan G. Duda
- Department of Radiation Oncology, Steele Laboratories, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - James C. Yao
- Department of Gastrointestinal Medical Oncology, M.D. Anderson Cancer Center, The University of Texas, Houston, TX, USA
| | - Michael LaPelusa
- Division of Cancer Medicine, M.D. Anderson Cancer Center, Houston, TX, USA
| | - Eugene J. Koay
- Department of Radiation Oncology, Division of Radiation Oncology, M.D. Anderson Cancer Center, The University of Texas, Houston, TX, USA
| | - Armeen Mahvash
- Department of Interventional Radiology, Division of Diagnostic Imaging, M.D. Anderson Cancer Center, Houston, TX, USA
| | - Ahmed Al Azzam
- Department of Radiation Oncology, Steele Laboratories, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Ecaterina E. Dumbrava
- Department of Interventional Radiology, Division of Diagnostic Imaging, M.D. Anderson Cancer Center, Houston, TX, USA
| | - Manal Hassan
- Department of Epidemiology, M.D. Anderson Cancer Center, The University of Texas, Houston, TX, USA
| | - Hesham M. Amin
- Department of Investigational Cancer Therapeutics, M.D. Anderson Cancer Center, The University of Texas, Houston, TX, USA
- UTHealth Graduate School of Biomedical Sciences, M.D. Anderson Cancer Center, Houston, TX, USA
| | - Ahmed Omar Kaseb
- Department of Gastrointestinal Medical Oncology, M.D. Anderson Cancer Center, The University of Texas, Houston, TX, USA
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4
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Zhou C, Weng J, Liu S, Zhou Q, Hu Z, Yin Y, Lv P, Sun J, Li H, Yi Y, Shen Y, Ye Q, Shi Y, Dong Q, Liu C, Zhu X, Ren N. Whole-exome sequencing reveals the metastatic potential of hepatocellular carcinoma from the perspective of tumor and circulating tumor DNA. Hepatol Int 2023; 17:1461-1476. [PMID: 37217808 DOI: 10.1007/s12072-023-10540-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Accepted: 04/15/2023] [Indexed: 05/24/2023]
Abstract
BACKGROUND Relapse of hepatocellular carcinoma (HCC) due to vascular invasion is common, but the genomic mechanisms remain unclear, and molecular determinants of high-risk relapse cases are lacking. We aimed to reveal the evolutionary trajectory of microvascular invasion (MVI) and develop a predictive signature for relapse in HCC. METHODS Whole-exome sequencing was performed on tumor and peritumor tissues, portal vein tumor thrombus (PVTT), and circulating tumor DNA (ctDNA) to compare the genomic profiles between 5 HCC patients with MVI and 5 patients without MVI. We conducted an integrated analysis of exome and transcriptome to develop and validate a prognostic signature in two public cohorts and one cohort from Zhongshan Hospital, Fudan University. RESULTS Shared genomic landscapes and identical clonal origins among tumor, PVTT, and ctDNA were observed in MVI ( +) HCC, suggesting that genomic changes favoring metastasis occur at the primary tumor stage and are inherited in metastatic lesions and ctDNA. There was no clonal relatedness between the primary tumor and ctDNA in MVI ( - ) HCC. HCC had dynamic mutation alterations during MVI and exhibited genetic heterogeneity between primary and metastatic tumors, which can be comprehensively reflected by ctDNA. A relapse-related gene signature named RGSHCC was developed based on the significantly mutated genes associated with MVI and shown to be a robust classifier of HCC relapse. CONCLUSIONS We characterized the genomic alterations during HCC vascular invasion and revealed a previously undescribed evolution pattern of ctDNA in HCC. A novel multiomics-based signature was developed to identify high-risk relapse populations.
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Affiliation(s)
- Chenhao Zhou
- Department of Liver Surgery and Transplantation, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People's Republic of China
- Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer of Shanghai Municipal Health Commission, Shanghai, 201199, People's Republic of China
| | - Jialei Weng
- Department of Liver Surgery and Transplantation, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People's Republic of China
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer of Shanghai Municipal Health Commission, Shanghai, 201199, People's Republic of China
| | - Shaoqing Liu
- Department of Liver Surgery and Transplantation, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People's Republic of China
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer of Shanghai Municipal Health Commission, Shanghai, 201199, People's Republic of China
| | - Qiang Zhou
- Department of Liver Surgery and Transplantation, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People's Republic of China
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer of Shanghai Municipal Health Commission, Shanghai, 201199, People's Republic of China
| | - Zhiqiu Hu
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer of Shanghai Municipal Health Commission, Shanghai, 201199, People's Republic of China
- Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, 201199, People's Republic of China
| | - Yirui Yin
- Department of Liver Surgery, Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, 361015, People's Republic of China
| | - Peng Lv
- Department of Liver Surgery, Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, 361015, People's Republic of China
| | - Jialei Sun
- Department of Liver Surgery and Transplantation, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People's Republic of China
| | - Hui Li
- Department of Liver Surgery and Transplantation, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People's Republic of China
| | - Yong Yi
- Department of Liver Surgery and Transplantation, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People's Republic of China
| | - Yinghao Shen
- Department of Liver Surgery and Transplantation, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People's Republic of China
| | - Qinghai Ye
- Department of Liver Surgery and Transplantation, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People's Republic of China
| | - Yi Shi
- Biomedical Research Centre, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China
| | - Qiongzhu Dong
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer of Shanghai Municipal Health Commission, Shanghai, 201199, People's Republic of China
- Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, 201199, People's Republic of China
| | - Chunxiao Liu
- Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA
| | - Xiaoqiang Zhu
- State Key Laboratory for Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, School of Medicine, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, Shanghai Jiao Tong University, Shanghai, 200001, People's Republic of China.
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, 999077, People's Republic of China.
| | - Ning Ren
- Department of Liver Surgery and Transplantation, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People's Republic of China.
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer of Shanghai Municipal Health Commission, Shanghai, 201199, People's Republic of China.
- Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, 201199, People's Republic of China.
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Manzi J, Hoff CO, Ferreira R, Glehn-Ponsirenas R, Selvaggi G, Tekin A, O'Brien CB, Feun L, Vianna R, Abreu P. Cell-Free DNA as a Surveillance Tool for Hepatocellular Carcinoma Patients after Liver Transplant. Cancers (Basel) 2023; 15:3165. [PMID: 37370775 PMCID: PMC10296050 DOI: 10.3390/cancers15123165] [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: 05/02/2023] [Revised: 05/30/2023] [Accepted: 06/09/2023] [Indexed: 06/29/2023] Open
Abstract
The liver is the world's sixth most common primary tumor site, responsible for approximately 5% of all cancers and over 8% of cancer-related deaths. Hepatocellular carcinoma (HCC) is the predominant type of liver cancer, accounting for approximately 75% of all primary liver tumors. A major therapeutic tool for this disease is liver transplantation. Two of the most significant issues in treating HCC are tumor recurrence and graft rejection. Currently, the detection and monitoring of HCC recurrence and graft rejection mainly consist of imaging methods, tissue biopsies, and alpha-fetoprotein (AFP) follow-up. However, they have limited accuracy and precision. One of the many possible components of cfDNA is circulating tumor DNA (ctDNA), which is cfDNA derived from tumor cells. Another important component in transplantation is donor-derived cfDNA (dd-cfDNA), derived from donor tissue. All the components of cfDNA can be analyzed in blood samples as liquid biopsies. These can play a role in determining prognosis, tumor recurrence, and graft rejection, assisting in an overall manner in clinical decision-making in the treatment of HCC.
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Affiliation(s)
- Joao Manzi
- School of Medicine, University of Sao Paulo, Sao Paulo 05508-900, Brazil
- Miami Transplant Institute, Jackson Memorial Hospital, University of Miami, Miami, FL 33136, USA
| | - Camilla O Hoff
- School of Medicine, University of Sao Paulo, Sao Paulo 05508-900, Brazil
- Miami Transplant Institute, Jackson Memorial Hospital, University of Miami, Miami, FL 33136, USA
| | - Raphaella Ferreira
- Miami Transplant Institute, Jackson Memorial Hospital, University of Miami, Miami, FL 33136, USA
| | | | - Gennaro Selvaggi
- Miami Transplant Institute, Jackson Memorial Hospital, University of Miami, Miami, FL 33136, USA
| | - Akin Tekin
- Miami Transplant Institute, Jackson Memorial Hospital, University of Miami, Miami, FL 33136, USA
| | - Christopher B O'Brien
- Miami Transplant Institute, Jackson Memorial Hospital, University of Miami, Miami, FL 33136, USA
| | - Lynn Feun
- Miami Transplant Institute, Jackson Memorial Hospital, University of Miami, Miami, FL 33136, USA
| | - Rodrigo Vianna
- Miami Transplant Institute, Jackson Memorial Hospital, University of Miami, Miami, FL 33136, USA
| | - Phillipe Abreu
- Miami Transplant Institute, Jackson Memorial Hospital, University of Miami, Miami, FL 33136, USA
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6
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Sajid M, Liu L, Sun C. The Dynamic Role of NK Cells in Liver Cancers: Role in HCC and HBV Associated HCC and Its Therapeutic Implications. Front Immunol 2022; 13:887186. [PMID: 35669776 PMCID: PMC9165341 DOI: 10.3389/fimmu.2022.887186] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Accepted: 04/12/2022] [Indexed: 11/21/2022] Open
Abstract
Hepatocellular carcinoma (HCC) remains an important complication of chronic liver disease, especially when cirrhosis occurs. Existing treatment strategies include surgery, loco-regional techniques, and chemotherapy. Natural killer cells are distinctive cytotoxic lymphocytes that play a vital role in fighting tumors and infections. As an important constituent of the innate immune system against cancer, phenotypic and functional deviations of NK cells have been demonstrated in HCC patients who also exhibit perturbation of the NK-activating receptor/ligand axis. The rate of recurrence of tumor-infiltrating and circulating NK cells are positively associated with survival benefits in HCC and have prognostic significance, suggesting that NK cell dysfunction is closely related to HCC progression. NK cells are the first-line effector cells of viral hepatitis and play a significant role by directly clearing virus-infected cells or by activating antigen-specific T cells by producing IFN-γ. In addition, chimeric antigen receptor (CAR) engineered NK cells suggest an exclusive opportunity to produce CAR-NKs with several specificities with fewer side effects. In the present review, we comprehensively discuss the innate immune landscape of the liver, particularly NK cells, and the impact of tumor immune microenvironment (TIME) on the function of NK cells and the biological function of HCC. Furthermore, the role of NK cells in HCC and HBV-induced HCC has also been comprehensively elaborated. We also elaborate on available NK cell-based immunotherapeutic approaches in HCC treatment and summarize current advancements in the treatment of HCC. This review will facilitate researchers to understand the importance of the innate immune landscape of NK cells and lead to devising innovative immunotherapeutic strategies for the systematic treatment of HCC.
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Affiliation(s)
- Muhammad Sajid
- Department of Hepatobiliary Surgery, Anhui Provincial Clinical Research Center for Hepatobiliary Diseases, Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Heifei, China
- Transplant and Immunology Laboratory, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Lianxin Liu
- Department of Hepatobiliary Surgery, Anhui Provincial Clinical Research Center for Hepatobiliary Diseases, Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Heifei, China
| | - Cheng Sun
- Department of Hepatobiliary Surgery, Anhui Provincial Clinical Research Center for Hepatobiliary Diseases, Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Heifei, China
- Transplant and Immunology Laboratory, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
- Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
- Institute of Immunology, University of Science and Technology of China, Hefei, China
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7
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Pelizzaro F, Kitenge MP, Cardin R, Ponzoni A, Cillo U, Vitale A, Businello G, Munari G, Fassan M, Farinati F. Circulating prostaglandin E 2: a novel potential prognostic biomarker in patients with hepatocellular carcinoma. Clin Exp Med 2021; 21:675-682. [PMID: 33768340 DOI: 10.1007/s10238-021-00705-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 03/17/2021] [Indexed: 02/07/2023]
Abstract
We aimed to explore the activation of monoacylglycerol lipase (MAGL)/cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) axis in hepatocellular carcinoma (HCC), evaluating circulating PGE2 as prognostic biomarker in HCC patients. PGE2 levels were measured in blood samples from 24 cirrhotics, and 34 HCC patients were consecutively collected between January 2016 and December 2017. In a subgroup of patients, tissue expression of MAGL mRNA and immunohistochemistry for MAGL and COX-2 were obtained. Despite tumor tissues showing overexpression of MAGL mRNA and higher levels of both MAGL and COX-2 at immunohistochemistry, PGE2 levels were not significantly different in HCC and cirrhotics. HCC patients with circulating PGE2 levels > 14 pg/mL had a significantly shorter overall survival (19.4 vs. 49.9 months; p = 0.03), the finding being confirmed by the multivariate analysis (HR 3.37 [95% CI 1.00-11.60]; p = 0.05). The MAGL/COX-2/PGE2 axis is activated in HCC, and circulating PGE2 proved to be a potential prognostic biomarker.
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Affiliation(s)
- Filippo Pelizzaro
- Gastroenterology Unit, Oncology and Gastroenterology, Department of Surgery, University of Padova, Padova, Italy
| | - Maria Piera Kitenge
- Gastroenterology Unit, Oncology and Gastroenterology, Department of Surgery, University of Padova, Padova, Italy
| | - Romilda Cardin
- Gastroenterology Unit, Oncology and Gastroenterology, Department of Surgery, University of Padova, Padova, Italy
| | - Alberto Ponzoni
- Radiology Unit, Azienda-Ospedale Università Di Padova, Padova, Italy
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplantation Unit, Oncology and Gastroenterology, Department of Surgery, University of Padova, Padova, Italy
| | - Alessandro Vitale
- Hepatobiliary Surgery and Liver Transplantation Unit, Oncology and Gastroenterology, Department of Surgery, University of Padova, Padova, Italy
| | - Gianluca Businello
- Surgical Pathology and Cytopathology Unit, Department of Medicine (DIMED), University of Padova, Padova, Italy
| | - Giada Munari
- Surgical Pathology and Cytopathology Unit, Department of Medicine (DIMED), University of Padova, Padova, Italy
| | - Matteo Fassan
- Surgical Pathology and Cytopathology Unit, Department of Medicine (DIMED), University of Padova, Padova, Italy
| | - Fabio Farinati
- Gastroenterology Unit, Oncology and Gastroenterology, Department of Surgery, University of Padova, Padova, Italy.
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8
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Karimi MR, Karimi AH, Abolmaali S, Sadeghi M, Schmitz U. Prospects and challenges of cancer systems medicine: from genes to disease networks. Brief Bioinform 2021; 23:6361045. [PMID: 34471925 PMCID: PMC8769701 DOI: 10.1093/bib/bbab343] [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: 05/04/2021] [Revised: 08/02/2021] [Accepted: 08/03/2021] [Indexed: 12/20/2022] Open
Abstract
It is becoming evident that holistic perspectives toward cancer are crucial in deciphering the overwhelming complexity of tumors. Single-layer analysis of genome-wide data has greatly contributed to our understanding of cellular systems and their perturbations. However, fundamental gaps in our knowledge persist and hamper the design of effective interventions. It is becoming more apparent than ever, that cancer should not only be viewed as a disease of the genome but as a disease of the cellular system. Integrative multilayer approaches are emerging as vigorous assets in our endeavors to achieve systemic views on cancer biology. Herein, we provide a comprehensive review of the approaches, methods and technologies that can serve to achieve systemic perspectives of cancer. We start with genome-wide single-layer approaches of omics analyses of cellular systems and move on to multilayer integrative approaches in which in-depth descriptions of proteogenomics and network-based data analysis are provided. Proteogenomics is a remarkable example of how the integration of multiple levels of information can reduce our blind spots and increase the accuracy and reliability of our interpretations and network-based data analysis is a major approach for data interpretation and a robust scaffold for data integration and modeling. Overall, this review aims to increase cross-field awareness of the approaches and challenges regarding the omics-based study of cancer and to facilitate the necessary shift toward holistic approaches.
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Affiliation(s)
| | | | | | - Mehdi Sadeghi
- Department of Cell & Molecular Biology, Semnan University, Semnan, Iran
| | - Ulf Schmitz
- Department of Molecular & Cell Biology, James Cook University, Townsville, QLD 4811, Australia
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9
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Fujii Y, Ono A, Hayes CN, Aikata H, Yamauchi M, Uchikawa S, Kodama K, Teraoka Y, Fujino H, Nakahara T, Murakami E, Miki D, Okamoto W, Kawaoka T, Tsuge M, Imamura M, Chayama K. Identification and monitoring of mutations in circulating cell-free tumor DNA in hepatocellular carcinoma treated with lenvatinib. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2021; 40:215. [PMID: 34174931 PMCID: PMC8235843 DOI: 10.1186/s13046-021-02016-3] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Accepted: 06/11/2021] [Indexed: 12/20/2022]
Abstract
Background There has been a recent surge in interest in predicting biological effects associated with genomic alterations in order to implement personalized cancer treatment strategies. However, no reports have yet evaluated the utility of profiling blood-based circulating tumor DNA (ctDNA) in hepatocellular carcinoma (HCC) patients treated with lenvatinib (LEN). Method We retrospectively performed ctDNA next-generation sequencing (NGS) analysis in 24 patients with advanced HCC at baseline and 4 weeks after initiation of LEN. Association of the changes in variant allele frequencies (VAFs) during treatment and clinical outcome were evaluated. Results In total, 131 single nucleotide variants, 17 indels, and 23 copy number variations were detected as somatic alterations in 28, 6, and 12 genes, respectively in 23 of 24 patients. The most frequently altered genes were TP53 (54%), CTNNB1 (42%), TERT (42%), ATM (25%), and ARID1A (13%). The reduction in the mean frequency of variants (VAFmean) following 4 weeks of LEN treatment was associated with longer progression-free survival. The specificity and sensitivity of the reduction of VAFmean for predicting partial response were 0.67 and 1.0, respectively, which were higher than those of serum α-fetoprotein level (0.10 and 0.93, respectively). No association between the mutation status at baseline and the effectiveness of LEN was observed. Conclusion Our study demonstrated that somatic alterations could be detected in the majority of advanced HCC patients by ctDNA profiling and that ctDNA-kinetics during LEN treatment was a useful marker of disease progression. These results suggest that ctDNA profiling is a promising method that provides valuable information in clinical practice. Supplementary Information The online version contains supplementary material available at 10.1186/s13046-021-02016-3.
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Affiliation(s)
- Yasutoshi Fujii
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
| | - Atsushi Ono
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
| | - C Nelson Hayes
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
| | - Hiroshi Aikata
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
| | - Masami Yamauchi
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
| | - Shinsuke Uchikawa
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
| | - Kenichiro Kodama
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
| | - Yuji Teraoka
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
| | - Hatsue Fujino
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
| | - Takashi Nakahara
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
| | - Eisuke Murakami
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
| | - Daiki Miki
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
| | - Wataru Okamoto
- Cancer Treatment Center, Hiroshima University Hospital, Hiroshima, Japan
| | - Tomokazu Kawaoka
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
| | - Masataka Tsuge
- Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima, Japan
| | - Michio Imamura
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
| | - Kazuaki Chayama
- Collaborative Research Laboratory of Medical Innovation, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. .,Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan. .,RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
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10
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RAP2A promotes apoptosis resistance of hepatocellular carcinoma cells via the mTOR pathway. Clin Exp Med 2021; 21:545-554. [PMID: 34018090 DOI: 10.1007/s10238-021-00723-x] [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: 11/17/2020] [Accepted: 05/06/2021] [Indexed: 12/24/2022]
Abstract
Hepatocellular carcinoma (HCC) is the most common digestive system cancer. In the current study, we investigated the biological effects of Ras-related protein Rap-2a (RAP2A), a GTPase protein, in HCC tissues and cells. We found that RAP2A was upregulated in HCC tissues and cells. RAP2A knockdown could effectively inhibit the proliferation of HCC cells and weaken its apoptosis resistance. In terms of its action mechanism, RAP2A may be involved in activating the mTOR signaling pathway. Therefore, we believe that RAP2A is abnormally highly expressed in HCC tissues and promotes tumor cell proliferation and apoptosis resistance by activating the mTOR signaling pathway, and it may serve as a potential target for HCC treatment.
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11
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Yao L, Xu H, Wo J, Zhao M, Liu Z, Dong T, Xiao S. Prognostic value of circulating tumor DNA in lymphoma: a meta-analysis. Clin Exp Med 2021; 22:1-7. [PMID: 33990849 DOI: 10.1007/s10238-021-00718-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 05/03/2021] [Indexed: 01/11/2023]
Abstract
Circulating tumor DNA (ctDNA) can be used to evaluate the prognosis of lymphoma. However, there is no uniform consensus about the mechanistic role that ctDNA plays in the prognosis of lymphoma. This meta-analysis explores the prognostic value of ctDNA in lymphoma, especially in diffuse large B cell lymphoma (DLBCL). All relevant reports published as of May 14, 2020, were retrieved by searching electronic databases in Pubmed, Embase and Cochrane Library. The prognostic value of ctDNA was evaluated using meta-analysis. Revman 5.3 software was used for prognostic data extraction and analysis. Eight studies, including a total of 767 lymphoma patients, were enrolled in this meta-analysis. Five out of eight studies investigated the association between ctDNA levels and progression-free survival (PFS) in 501 lymphoma patients, indicating that high levels of ctDNA were significantly associated with poor PFS (HR 2.24, 95%CI: 1.63-3.08, P < 0.00001). We conducted a subgroup analysis of 379 patients with DLBCL across three of the studies and came to the same conclusion (HR 2.01, 95%CI: 1.42-2.85, P < 0.0001). Two studies with a total of 192 lymphoma patients described the association between ctDNA levels and event-free survival (EFS), showing that high levels of ctDNA were also associated with adverse EFS (HR 4.53, 95%CI: 1.79-11.47, P = 0.001). The remaining two studies analyzed the potential clinical value of ctDNA for predicting the overall survival time (OS) of DLBCL patients, demonstrating that high levels of ctDNA correlated with inferior OS (HR 3.09, 95%CI: 1.50-6.35, P = 0.002). Our meta-analysis showed that high levels of ctDNA were associated with poor prognosis in patients with lymphoma, especially DLBCL.
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Affiliation(s)
- Laiyu Yao
- Department of Medicine, Medical College of Qingdao University, 266003, Qingdao, China
| | - Hong Xu
- Department of Hematology, The Affiliated Hospital of Qingdao University, 266003, Qingdao, China
| | - Jinshan Wo
- Department of Cardiovascular Medicine, The Affiliated Hospital of Qingdao University, 266003, Qingdao, China
| | - Meiqing Zhao
- Department of Hematology, Eighth People's Hospital of Qingdo, 266003, Qingdao, China
| | - Zhihe Liu
- Department of Hematology, The Affiliated Hospital of Qingdao University, 266003, Qingdao, China
| | - Tieying Dong
- Department of Hematology, The Affiliated Hospital of Qingdao University, 266003, Qingdao, China
| | - Shuxin Xiao
- Department of Hematology, The Affiliated Hospital of Qingdao University, 266003, Qingdao, China.
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12
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Li Y, Zheng Y, Wu L, Li J, Ji J, Yu Q, Dai W, Feng J, Wu J, Guo C. Current status of ctDNA in precision oncology for hepatocellular carcinoma. J Exp Clin Cancer Res 2021; 40:140. [PMID: 33902698 PMCID: PMC8074474 DOI: 10.1186/s13046-021-01940-8] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 04/06/2021] [Indexed: 01/12/2023] Open
Abstract
The conventional method used to obtain a tumor biopsy for hepatocellular carcinoma (HCC) is invasive and does not evaluate dynamic cancer progression or assess tumor heterogeneity. It is thus imperative to create a novel non-invasive diagnostic technique for improvement in cancer screening, diagnosis, treatment selection, response assessment, and predicting prognosis for HCC. Circulating tumor DNA (ctDNA) is a non-invasive liquid biopsy method that reveals cancer-specific genetic and epigenetic aberrations. Owing to the development of technology in next-generation sequencing and PCR-based assays, the detection and quantification of ctDNA have greatly improved. In this publication, we provide an overview of current technologies used to detect ctDNA, the ctDNA markers utilized, and recent advances regarding the multiple clinical applications in the field of precision medicine for HCC.
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Affiliation(s)
- Yan Li
- Department of Gastroenterology, Putuo People's Hospital, Tongji University School of Medicine, number 1291, Jiangning road, Putuo, Shanghai, 200060, China
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Number 301, Middle Yanchang road, Jing'an, Shanghai, 200072, China
| | - Yuanyuan Zheng
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Number 301, Middle Yanchang road, Jing'an, Shanghai, 200072, China
| | - Liwei Wu
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Number 301, Middle Yanchang road, Jing'an, Shanghai, 200072, China
| | - Jingjing Li
- Department of Gastroenterology, Putuo People's Hospital, Tongji University School of Medicine, number 1291, Jiangning road, Putuo, Shanghai, 200060, China
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Number 301, Middle Yanchang road, Jing'an, Shanghai, 200072, China
| | - Jie Ji
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Number 301, Middle Yanchang road, Jing'an, Shanghai, 200072, China
| | - Qiang Yu
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Number 301, Middle Yanchang road, Jing'an, Shanghai, 200072, China
| | - Weiqi Dai
- Department of Gastroenterology, Putuo People's Hospital, Tongji University School of Medicine, number 1291, Jiangning road, Putuo, Shanghai, 200060, China
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Number 301, Middle Yanchang road, Jing'an, Shanghai, 200072, China
| | - Jiao Feng
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Number 301, Middle Yanchang road, Jing'an, Shanghai, 200072, China.
| | - Jianye Wu
- Department of Gastroenterology, Putuo People's Hospital, Tongji University School of Medicine, number 1291, Jiangning road, Putuo, Shanghai, 200060, China.
| | - Chuanyong Guo
- Department of Gastroenterology, Putuo People's Hospital, Tongji University School of Medicine, number 1291, Jiangning road, Putuo, Shanghai, 200060, China.
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Number 301, Middle Yanchang road, Jing'an, Shanghai, 200072, China.
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13
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Weng J, Zhou C, Zhou Q, Chen W, Yin Y, Atyah M, Dong Q, Shi Y, Ren N. Development and Validation of a Metabolic Gene-Based Prognostic Signature for Hepatocellular Carcinoma. J Hepatocell Carcinoma 2021; 8:193-209. [PMID: 33824863 PMCID: PMC8018394 DOI: 10.2147/jhc.s300633] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Accepted: 02/23/2021] [Indexed: 12/12/2022] Open
Abstract
Background Hepatocellular carcinoma (HCC) is a malignant tumor with great variation in prognosis among individuals. Changes in metabolism influence disease progression and clinical outcomes. The objective of this study was to determine the overall survival (OS) risk of HCC patients from a metabolic perspective. Patients and Methods The model was constructed using the least absolute shrinkage and selection operator (LASSO) COX regression based on The Cancer Genome Atlas (TCGA, n=342) dataset. The International Cancer Genome Consortium (ICGC, n=232), GSE14520 (n=242) datasets, and a clinical cohort (n=64) were then used to assess the prognostic value of the signature. Results A 10 metabolic gene-based signature was constructed and verified as a robust and independent prognostic classifier in public and real-world validation cohorts. Meanwhile, the signature enabled the identification of HCC molecular subtypes, yielding an AUC value of 0.678 [95% CI: 0.592–0.763]. Besides, the signature was associated with metabolic processes like glycolysis, supported by a clear correlation between the risk score and expression of rate-limiting enzymes. Furthermore, high-risk tumor was likely to have a high tumor infiltration status of immunosuppressive cells, as well as elevated expression of some immune checkpoint molecules. For final clinical translation, a nomogram integrating the signature and tumor stage was established, and showed improved predictive accuracy of 3- and 5-year OS and brought more net benefit to patients. Conclusion We developed a prognostic signature based on 10 metabolic genes, which has proven to be an independent and reliable prognostic predictor for HCC and reflects the metabolic and immune characteristics of tumors.
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Affiliation(s)
- Jialei Weng
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, People's Republic of China
| | - Chenhao Zhou
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, People's Republic of China.,Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Qiang Zhou
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, People's Republic of China
| | - Wanyong Chen
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, People's Republic of China.,Institute of Fudan Minhang Academic Health System, Minhang Hospital, Key Laboratory of Shanghai Municipal Health Commission, Fudan University, Shanghai, People's Republic of China
| | - Yirui Yin
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, People's Republic of China
| | - Manar Atyah
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, People's Republic of China
| | - Qiongzhu Dong
- Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.,Institute of Fudan Minhang Academic Health System, Minhang Hospital, Key Laboratory of Shanghai Municipal Health Commission, Fudan University, Shanghai, People's Republic of China.,Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China
| | - Yi Shi
- Biomedical Research Centre, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Ning Ren
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, People's Republic of China.,Institute of Fudan Minhang Academic Health System, Minhang Hospital, Key Laboratory of Shanghai Municipal Health Commission, Fudan University, Shanghai, People's Republic of China
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14
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Chan LK, Tsui YM, Ho DWH, Ng IOL. Cellular heterogeneity and plasticity in liver cancer. Semin Cancer Biol 2021; 82:134-149. [PMID: 33647386 DOI: 10.1016/j.semcancer.2021.02.015] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Accepted: 02/22/2021] [Indexed: 02/07/2023]
Abstract
Hepatocarcinogenesis involves complex genetic and cellular dysregulations which drive the formation of hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, with extensive heterogeneity. In contrast to the broad spectrum of molecularly driven therapies available for defined patient groups in certain cancer types, unfortunately the treatment options for HCC are highly limited. The lack of representative molecular and cellular signatures in the heterogeneous HCC tumors that can effectively guide the choice of the most appropriate treatment among the patients unavoidably limits the treatment outcome. Advancement and wide availability of the next-generation sequencing technologies have empowered us to examine and capture not only the detailed genetic alterations of the HCC cells but also the precise composition of different cell types within the tumor microenvironment and their interactions with the HCC cells at an unprecedented level. The information generated has provided new insight and better defined the inter-patient intertumoral heterogeneity, intra-patient intratumoral heterogeneity as well as the plasticity of HCC cells. These collectively provide a robust scientific basis in guiding the development and use of targeted therapy and immunotherapy. To complement, liquid biopsy coupled with high-sensitivity sequencing could potentially be adopted as a more practical and safer approach to detect and reflect the tumor heterogeneity in HCC patients in guiding the choice of treatment and monitoring disease progression.
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Affiliation(s)
- Lo-Kong Chan
- Department of Pathology, The University of Hong Kong, Hong Kong; State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong
| | - Yu-Man Tsui
- Department of Pathology, The University of Hong Kong, Hong Kong; State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong
| | - Daniel Wai-Hung Ho
- Department of Pathology, The University of Hong Kong, Hong Kong; State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong
| | - Irene Oi-Lin Ng
- Department of Pathology, The University of Hong Kong, Hong Kong; State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong.
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