Comparison of key genes regulating the prognosis of HBV/HCV-related hepatocellular carcinoma

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Despite the decrease in both incidence and mortality rates in the last few years, Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infection account for 70% of global liver cancer deaths. However, few researches have explored the prognostic similarities and differences between HBV-related HCC (HBV-HCC) and HCV-related HCC (HCV-HCC) at transcript level. Therefore, we aim to identify genes that may play an important role in regulating prognosis for HBV-HCC and HCV-HCC respectively and potentially lead to the prognostic difference between HBV-HCC and HCV-HCC. Methods Weighted correlation network analysis (WGCNA) was first conducted to identify gene modules related with prognosis using The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) cohort. The K-means clustering algorithm, Univariate and Multivariate Cox regression were, in turn, used to identify hub gene related to prognosis. The hub genes were then validated using ICGC-LIRI-JP cohort from The International Cancer Genome Consortium(ICGC) database by Multivariate Cox regression. Lastly, the validated genes in each group were alternately validated in other group. Results Midnightblue and paleturquoise modules in HBV group, greenyellow and white modules in HCV group were selected during WGCNA. Later, CALCRL, TMEM204, APLNR, MED8, HSPB11, TRAPPC3, ADPRS and BTF3L4 in HBV group, NEU1, DHX16, EDEM3, GLRX2 and CYB5R1 in HCV group were screened as our hub genes. Eventually, during validation phase, TMEM204 remained significant in both groups, and CYB5R1 was only significant in HCV group. Conclusions Our study suggested that there may be substantial prognostic differences between HBV-HCC and HCV-HCC in terms of mechanism. CYB5R1 may be partially related to prognostic difference between HBV-HCC and HCV-HCC.