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Custom gene expression panel for evaluation of potential molecular markers in hepatocellular carcinoma

Thirumalaisamy P. (16302666200) | Le Huu (7402537840); Velavan | Mai Hong (57201733456); Song | Peter G. (35459833700); Bang | Dao Phuong (57191610748); Kremsner | Le Thi Kieu (57219052608); Giang | Nguyen Linh (14029367600); Linh | Hoang (35742255000); Toan Faculty of Gastroenterology, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Viet Nam| Sivaramakrishna (57316352700); Meyer Vietnam Military Medical University, Hanoi, Viet Nam| Nghiem Xuan (56053401600); Rachakonda Department of Molecular Biology, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Viet Nam| Srinivas Reddy (57212444558); Hoan Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Viet Nam|

BMC Medical Genomics Số 1, năm 2022 (Tập 15, trang -)

ISSN: 17558794

ISSN: 17558794

DOI: 10.1186/s12920-022-01386-7

Tài liệu thuộc danh mục:



Từ khóa: alpha-Fetoproteins; Biomarkers, Tumor; Carcinoma, Hepatocellular; Gene Expression; Gene Expression Regulation, Neoplastic; Glypicans; Humans; Liver Neoplasms; Prognosis; alpha fetoprotein; baculoviral IAP repeat containing protein 5; CA 19-9 antigen; carcinoembryonic antigen; catenin; cell cycle protein 20; cyclin dependent kinase 1; DNA topoisomerase (ATP hydrolysing) B; glyceraldehyde 3 phosphate dehydrogenase (NADP)(phosphorylating); glypican 3; isocitrate dehydrogenase 1; molecular marker; programmed death 1 ligand 1; protein mcl 1; protein MDMX; protein p53; Raf protein; retinoblastoma binding protein 1; scatter factor receptor; somatomedin A; TATA binding protein; telomerase reverse transcriptase; tumor marker; vasculotropin A; Wnt protein; alpha fetoprotein; glypican; GPC3 protein, human; adult; AFP gene; ARID1A gene; Article; BIRC5 gene; c MET gene; cancer diagnosis; cancer prognosis; cancer therapy; CDK1 gene; clinical article; cohort analysis; controlled study; CTNNB1 gene; female; gene cluster; gene expression; gene expression profiling; gene identification; GLUL1 gene; GPC3 gene; Hepatitis B virus; hierarchical clustering; human; human cell; human tissue; IGF2 gene; LGR5 gene; liver cell carcinoma; male; marker gene; panel study; prediction; RAF1 gene; retrospective study; signal transduction; somatic mutation; TERT gene; TOP2A gene; treatment outcome; tumor gene; tumor growth; Viet Nam; Vietnamese; gene expression; gene expression regulation; genetics; liver tumor; metabolism; pathology; prognosis
Tóm tắt tiếng anh
Background: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide. It is a highly heterogeneous disease with poor prognosis and limited treatment options, which highlights the need for reliable biomarkers. This study aims to explore molecular markers that allow stratification of HCC and may lead to better prognosis and treatment prediction. Materials and methods: We studied 20 candidate genes (HCC hub genes, potential drug target genes, predominant somatic mutant genes) retrieved from literature and public databases with potential to be used as the molecular markers. We analysed expression of the genes by RT-qPCR in 30 HCC tumour and adjacent non-tumour paired samples from Vietnamese patients. Fold changes in expression were then determined using the 2−∆∆CT method, and unsupervised hierarchical clustering was generated using Cluster v3.0 software. Results: Clustering of expression data revealed two subtypes of tumours (proliferative and normal-like) and four clusters for genes. The expression profiles of the genes TOP2A, CDK1, BIRC5, GPC3, IGF2, and AFP were strongly correlated. Proliferative tumours were characterized by high expression of the c-MET, ARID1A, CTNNB1, RAF1, LGR5, and GLUL1 genes. TOP2A, CDK1, and BIRC5 HCC hub genes were highly expressed (> twofold) in 90% (27/30), 83% (25/30), and 83% (24/30) in the tissue samples, respectively. Among the drug target genes, high expression was observed in the GPC3, IGF2 and c-MET genes in 77% (23/30), 63% (19/30), and 37% (11/30), respectively. The somatic mutant Wnt/ß-catenin genes (CTNNB1, GLUL and LGR5) and TERT were highly expressed in 40% and 33% of HCCs, respectively. Among the HCC marker genes, a higher percentage of tumours showed GPC3 expression compared to AFP expression [73% (23/30) vs. 43% (13/30)]. Conclusion: The custom panel and molecular markers from this study may be useful for diagnosis, prognosis, biomarker-guided clinical trial design, and prediction of treatment outcomes. © 2022, The Author(s).

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