Background: Hepatocellular carcinoma (HCC) is one of the majorcause of cancer related deaths worldwide, due tohigh 5 yearpostoperativerecurrence rate and individualheterogeneity.Thus, prognostic modelhas dramaticallyurgently neededon HCCin recent years.Serval research have reported that copy number amplificationof the 8q24 chromosomalregion is associated with lowsurvival in many cancers. The objectiveof this study was to construct a multi-gene modelto predict the prognosis of HCC.
Methods: RNAseq and copy number variant (CNV)data of tumor tissue samples of HCC from TCGA(N = 328)wasused to identify differentially expressed mRNAs of genes located on chromosomal 8q24 regionsby Wilcoxtest.Univariate Cox and Lasso Cox regressionwereperformed to screenand constructprognostic multi-gene signature in TCGA cohort (N = 119). The multi-gene signature was validated in ICGCcohort(N = 240).A nomogram for prognosis prediction was built and Gene Set Enrichment Analysis (GSEA) was usedto further studythe underlying molecular mechanisms.
Results:A 7-gene prognosis signaturemodelwas established for predicting HCC prognosis. Using the model, we divided individualsinto high-risk and low-risk setswith significantly different overall survival in training dataset(HR = 0.17, 95% CI 0.1–0.28; P ＜0.001) and in testing dataset (HR = 0.42, 95% CI 0.23–0.74; P =0.002). Multivariate Cox regression analysis indicatedthat thissignature was an independentprognostic factor ofHCC survival. Nomogram including the prognostic signature was constructed and showed better predictive performance in short year (1and 3year) than long year (5 year) survival. Furthermore, GSEA revealed several significantly pathways, which may help explain the underlying molecular mechanism.
Conclusions:The 7-gene signature was areliableprognosticmarkerinHCC, which may provide meaningful informationto therapeutic customization and treatment decision making.