Gene-based cancer-testis antigens as prognostic indicators in hepatocellular carcinoma

Cancer/testis antigens (CTAs) are reproductive tissue-restricted genes, frequently ectopic expressed in tumors. CTA genes associate with a poor prognosis in some solid tumors, due to their potential roles in the tumorigenesis and progression. However, whether CTAs relate with hepatocellular carcinoma (HCC) remains unclear. In this study, the prognostic signatures based on CTA genes were investigated and validated in three cohorts including Chinese HCC patients with hepatitis B virus infection (CHCC-HBV), International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) cohorts. Univariate, LASSO, and multivariate Cox regression analyses were used to screen prognostic genes and develop the prognostic gene signature. A prognosis model was established with six CTA genes (SSX1, CTCFL, OIP5, CEP55, NOL4, and TPPP2) in CHCC-HBV cohort, and further validated in the ICGC and TCGA cohorts. The CTA signature was an essential prognostic predictor independent of other clinical pathological factors. High-risk group exhibited up-regulated cell cycle-related and tumor-related pathways and more M0 macrophage, activated mast cell, activated memory CD4⁺ T cell, and memory B cell infiltration. Furthermore, CTA signature correlated with the sensitivity to multiple chemotherapy drugs. Our results highlighted that the CTA gene profiling was a prognostic assessment tool for HCC patients.