| International Session（Symposium）3(JSGS・JSGE・JSH・JSGCS) |
| Fri. November 22nd 14:00 - 16:30 Room 2: Kobe International Exhibition Hall No.2 Building Hall (South) |
| Integrative multi-omics approach to explore novel biomarkers for hepatocarcinogenesis after eradication of hepatitis C virus. | |||
| Haruhiko Takeda1, Atsushi Takai1, Hiroshi Seno1 | |||
| 1Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University | |||
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| Aims: Little is known about the genomic and transcriptomic features of hepatocellular carcinoma arising after HCV eradication (SVR-HCC). In this study, we aimed to unveil the genomic and transcriptomic basis of hepatocarcinogenesis after SVR and to explore novel biomarkers to predict the risk of SVR-HCC. Methods: We first examined genetic alterations of tumors in 12 cases with SVR-HCC using whole-exome sequencing, target-deep sequencing of cancer-related genes and array-based whole-genome copy number analysis. Then, RNA-sequencing was conducted for background liver tissues of SVR-HCC cases to examine the candidate transcriptional biomarkers associated with hepatocarcinogenesis after SVR. Results: Genetic analyses revealed that mutation rates, mutational signatures, mutated driver genes and copy number alterations in SVR-HCC were quite similar to HCV-positive HCCs. As to transcriptome analysis, clustering of differentially expressed genes let us detect a gene cluster whose expression level was suppressed in normal livers and significantly elevated in HCV-positive cases as well as SVR-HCC cases. Interestingly, this cluster included several hepatocarcinogenesis-associated genes, whose expression profiles could represent the malignant potential of noncancerous tissues of SVR-HCC. Conclusion: Genomic analysis indicated that oncogenic pathways of SVR-HCC are identical to those of HCV-positive HCCs. On the other hand, comprehensive transcriptome analysis using non-cancerous liver tissue revealed candidate molecules for possible biomarkers in hepatocarcinogenesis after SVR achievement. |
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Index Term 1: genetic analysis Index Term 2: hepatocellular carcinoma |
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