The Outcomes and Next Landscapes of Project HOPE (High-Tech Omics-Based Patient Evaluation) for Hepatocellular Carcinoma

Abstract

Introduction: Project HOPE (High-tech Omics-based Patient Evaluation) aims to provide the multiomics data of cancer patients for the promotion of individualized medicine and the practice of prophylaxis. To reveal the relationship between the clinical data and genetic expression, genetic analyses based on the results of project HOPE were performed for 24 patients who underwent hepatectomy for hepatocellular carcinoma (HCC). Methods: Fresh surgical specimens obtained from HCC patients who underwent surgery at the Shizuoka Cancer Center Hospital, were analyzed by whole-exon sequencing (WES, Life Technologies) and gene expression profiling (GEP, Agilent Technologies). As of April 1, 2015, 24 patients have been analyzed, and the aberrant genes were identified from the results of the WES and GEP analyses. Results: The present study included 17 males and 7 females, with a median age of 67 years (range: 42-81 years). Six of the patients were positive for hepatitis B surface antigen, 9 were positive for hepatitis C antibody and 9 patients were negative for hepatitis virus infection. The WES analysis showed that specific single nucleotide variants (SNVs) were identified in the genes of CTNNB1 and TP53 at a frequency of 15% and 11%, respectively. The GEP analysis revealed the upregulation of the HIST1H3B (59%), EZH2 (33%) and MYCN (22%) genes in tumor tissue (in comparison to normal tissue), while the expressions of CDH1 (11%) and SOCS1 (11%) were found to be downregulated in tumor tissue. In the analysis of the association between the clinical data and gene expression, the rate of advanced tumor staging (UICC stage > 2) was significantly higher in the patients with upregulated HIST1H3B expression in tumor tissue than in those with normal HIST1H3B expression (57.1% vs. 10%, P=0.033). Moreover, the relapse-free survival rate of the patients with upregulated HIST1H3B expression of tumor tissue was significantly lower than that of patients with normal HIST1H3B expression (estimated median relapse-free survival time: 5.8 vs. 7.7 months; P=0.009). Conclusion: Our genetic analysis based on the results of Project HOPE revealed HIST1H3B to be novel cancer-related gene and a predictive factor for HCC. In the future, we plan to accumulate the results of 150 HCC patients, and it is hoped that the additional novel cancer-related genes will be identified.