Resampling based on geographic patterns of hepatitis virus infection reveals a common gene signature for early intrahepatic recurrence of hepatocellular carcinoma.

The majority of hepatocellular carcinomas (HCCs) correlated with infection by either hepatitis B or C virus (HBV or HCV) showing various geographic distributions, making it impossible to identify common gene signatures responsible for HCC recurrence. In this study we performed in silico resampling analysis of DNA microarray data that can reproduce virtually the geographic distribution pattern of HBV and HCV in 6 representative geographic regions. With the use of the Fisher ratio, genes associated with early intrahepatic recurrence of HCC within 1 year of surgery were identified in the 6 geographic virtual cohorts, each consisting of 1,000 virtual samples. The top 100 genes among each virtual cohort were compared. Many human leukocyte antigen (HLA) family genes were common among the 6 geographic virtual cohorts, suggesting that this gene family represents the pathway most responsible for early intrahepatic recurrence of HCC worldwide. This resampling approach is useful for identifying common pathways involved in various aspects of HCC.