Abstract
Hepatocellular carcinoma (HCC) is one of the most aggressive and dismal cancers globally. Emerging evidence has established that mTOR and Hippo pathways are oncogenic drivers of HCC. However, the prognostic value of these pathways in HCC remains unclear. In this study, we aimed to develop a gene signature utilizing the mTOR/Hippo genes for HCC prognostication. A multiple stage strategy was employed to screen, and a 12-gene signature based on mTOR/Hippo pathways was constructed to predict the prognosis of HCC patients. The risk scores calculated by the signature were inversely correlated with patient prognosis. Validation of the signature in independent cohort confirmed its predictive power. Further analysis revealed molecular differences between high and low-risk groups at genomic, transcriptomic, and protein-interactive levels. Moreover, immune infiltration analysis revealed an immunosuppressive state in the high-risk group. Finally, the gene signature could predict the sensitivity to current chemotherapeutic drugs. This study demonstrated that combinatorial mTOR/Hippo gene signature was a robust and independent prognostic tool for survival prediction of HCC. Our findings not only provide novel insights for the molecular understandings of mTOR/Hippo pathways in HCC, but also have important clinical implications for guiding therapeutic strategies.