Dataset Information

MicroRNAs as possible biomarkers for diagnosis and prognosis of hepatitis B- and C-related-hepatocellular-carcinoma.

ABSTRACT: Aim of the present review is to summarize the current knowledge about the potential relationship between miRNAs and hepatitis B virus (HBV)-hepatitis C virus (HCV) related liver diseases. A systematic computer-based search of published articles, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis Statement, was performed to identify relevant studies on usefulness of serum/plasma/urine miRNAs, as noninvasive biomarkers for early detection of HBV and HCV-induced hepatocellular carcinoma (HCC) development, as well as for its prognostic evaluation. The used Medical Subject Headings terms and keywords were: "HBV", "HCV", "hepatocellular carcinoma", "microRNAs", "miRNAs", "diagnosis", "prognosis", "therapy", "treatment". Some serum/plasma miRNAs, including miR-21, miR-122, mi-125a/b, miR-199a/b, miR-221, miR-222, miR-223, miR-224 might serve as biomarkers for early diagnosis/prognosis of HCC, but, to date, not definitive results or well-defined panels of miRNAs have been obtained. More well-designed studies, focusing on populations of different geographical areas and involving larger series of patients, should be carried out to improve our knowledge on the potential role of miRNAs for HCC early detection and prognosis.

SUBMITTER: Fiorino S

PROVIDER: S-EPMC4823242 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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MicroRNAs as possible biomarkers for diagnosis and prognosis of hepatitis B- and C-related-hepatocellular-carcinoma.

Fiorino Sirio S Bacchi-Reggiani Maria Letizia ML Visani Michela M Acquaviva Giorgia G Fornelli Adele A Masetti Michele M Tura Andrea A Grizzi Fabio F Zanello Matteo M Mastrangelo Laura L Lombardi Raffaele R Di Tommaso Luca L Bondi Arrigo A Sabbatani Sergio S Domanico Andrea A Fabbri Carlo C Leandri Paolo P Pession Annalisa A Jovine Elio E de Biase Dario D

World journal of gastroenterology 20160401 15

Aim of the present review is to summarize the current knowledge about the potential relationship between miRNAs and hepatitis B virus (HBV)-hepatitis C virus (HCV) related liver diseases. A systematic computer-based search of published articles, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis Statement, was performed to identify relevant studies on usefulness of serum/plasma/urine miRNAs, as noninvasive biomarkers for early detection of HBV and HCV-induced hep ...[more]

PMID: 27099435

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Project description:Circulating microRNAs are deregulated in liver fibrosis and hepatocellular carcinoma (HCC) and are candidate biomarkers. This study investigated the potential of serum microRNAs; miR-19a, miR-296, miR-130a, miR-195, miR-192, miR-34a, and miR-146a as early diagnostic biomarkers for hepatitis C virus (HCV)-related HCC. As how these microRNAs change during liver fibrosis progression is not clear, we explored their serum levels during fibrosis progression in HCV-associated chronic liver disease (CLD) and if they could serve as non-invasive biomarkers for fibrosis progression to HCC. 112 Egyptian HCV-HCC patients, 125 non-malignant HCV-CLD patients, and 42 healthy controls were included. CLD patients were subdivided according to Metavir fibrosis-scoring. Serum microRNAs were measured by qRT-PCR custom array. Serum microRNAs were deregulated in HCC versus controls, and except miR-130a, they were differentially expressed between HCC and CLD or late fibrosis (F3-F4) subgroup. Serum microRNAs were not significantly different between individual fibrosis-stages or between F1-F2 (early/moderate fibrosis) and F3-F4. Only miR-19a was significantly downregulated from liver fibrosis (F1-F3) to cirrhosis (F4) to HCC. Individual microRNAs discriminated HCC from controls, and except miR-130a, they distinguished HCC from CLD or F3-F4 patients by receiver-operating-characteristic analysis. Multivariate logistic analysis revealed a panel of four microRNAs (miR-19a, miR-195, miR-192, and miR-146a) with high diagnostic accuracy for HCC (AUC = 0.946). The microRNA panel also discriminated HCC from controls (AUC = 0.949), CLD (AUC = 0.945), and F3-F4 (AUC = 0.955). Studied microRNAs were positively correlated in HCC group. miR-19a and miR-34a were correlated with portal vein thrombosis and HCC staging scores, respectively. In conclusion, studied microRNAs, but not miR-130a, could serve as potential early biomarkers for HCC in high-risk groups, with miR-19a as a biomarker for liver fibrosis progression to cirrhosis to HCC. We identified a panel of four serum microRNAs with high accuracy in HCC diagnosis. Additional studies are required to confirm this panel and test its prognostic significance.

Project description:Introduction: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide due to poor survival outcome. Thus, there is an urgent need to identify effective biomarkers for early diagnosis and prognosis prediction. Methods: A total of 389 differentially expressed genes (DEGs) between HCC samples and normal were selected based on the Robust Rank Aggregation (RRA) method. We combined DEGs expression and clinical traits to construct a gene co-expression network through WGCNA. Forty hub genes were selected from the key module. Among them, YWHAB, PPAT, NOL10 were eventually identified as prognostic biomarkers using multivariate Cox regression model. Biomarkers expression pattern was investigated by informatic analysis and verified by RNA-seq of 32 patients with HCC. DiseaseMeth 2.0, MEXPRESS, and Tumor Immune Estimation Resource (TIMER) were used to assess the methylation and immune status of biomarkers. GSVA, CCK8, colony formation assay, Edu imaging kit, wound-healing assay, and xenograft tumor model were utilized to investigate the effects of biomarkers on proliferation, metastasis of HCC cells in vitro, and in vivo. The Kaplan-Meier (KM) plotter and ROC curves were used to validate the prognostic and diagnostic value of biomarker expression. Results: All the selected biomarkers were upregulated in HCC samples and higher expression levels were associated with advanced tumor stages and T grades. The regulation of YWHAB, PPAT, NOL10 promoter methylation varied in tumors, and precancerous normal tissues. Immune infiltration analysis suggested that the abnormal regulations of these biomarkers were likely attributed to B cells and dendritic cells. GSVA for these biomarkers showed their great contributions to proliferation of HCC. Specific inhibition of their expression had strong effects on tumorigenesis in vitro and in vivo. ROC and KM curves confirmed their usefulness of diagnosis and prognosis of HCC. Conclusions: These findings identified YWHAB, PPAT, and NOL10 as novel biomarkers and validated their diagnostic and prognostic value for HCC.

Project description:Hepatocellular carcinoma (HCC) is a common malignant cancer with poor survival outcomes, and hepatitis B virus (HBV) infection is most likely to contribute to HCC. But the molecular mechanism remains obscure. Our study intended to identify the candidate potential hub genes associated with the carcinogenesis of HBV-related HCC (HBV-HCC), which may be helpful in developing novel tumor biomarkers for potential targeted therapies. Four transcriptome datasets (GSE84402, GSE25097, GSE94660, and GSE121248) were used to screen the 309 overlapping differentially expressed genes (DEGs), including 100 upregulated genes and 209 downregulated genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were used to explore the biological function of DEGs. A PPI network based on the STRING database was constructed and visualized by the Cytoscape software, consisting of 209 nodes and 1676 edges. Then, we recognized 17 hub genes by CytoHubba plugin, which were further validated on additional three datasets (GSE14520, TCGA-LIHC, and ICGC-LIRI-JP). The diagnostic effectiveness of hub genes was assessed with receiver operating characteristic (ROC) analysis, and all hub genes displayed good performance in discriminating TNM stage I patient samples and normal tissue ones. For prognostic analysis, two prognostic key genes (TOP2A and KIF11) out of the 17 hub genes were screened and used to develop a prognostic signature, which showed good potential for overall survival (OS) stratification of HBV-HCC patients. Gene Set Enrichment Analysis (GSEA) was performed in order to better understand the function of this prognostic gene signature. Finally, the miRNA-mRNA regulatory relationships of all hub genes in human liver were predicted using miRNet. In conclusion, the current study gives further insight on the pathogenesis and carcinogenesis of HBV-HCC, and the identified DEGs provide a promising direction for improving the diagnostic, prognostic, and therapeutic outcomes of HBV-HCC.

Dataset Information

MicroRNAs as possible biomarkers for diagnosis and prognosis of hepatitis B- and C-related-hepatocellular-carcinoma.

Publications

MicroRNAs as possible biomarkers for diagnosis and prognosis of hepatitis B- and C-related-hepatocellular-carcinoma.

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