Comprehensive molecular profiling and clinicopathological analysis to predict response to pembrolizumab in advanced hepatocellular carcinoma

Reliable biomarkers help to monitor the patients’ response to immunotherapy and improve patient outcomes in many cancers. No such biomarkers are available for hepatocellular carcinoma (HCC). We characterized the molecular and clinicopathological profiles in 60 patients with HCC who were treated with pembrolizumab after sorafenib failure by whole-exome sequencing, RNA-seq analysis, and immunohistochemistry. Our results showed that CTNNB1 mutations, molecular signatures associated with proliferation, EMT and WNT, PD-L1 expression, and alpha-fetoprotein levels could be predictive biomarkers in certain patient subsets. Hence, the potential biomarkers reported in previous and the current study should be validated in future studies designed by adopting the biomarker-driven approach rather than the all-comers strategy.