Identification of hepatocellular carcinoma risk using a novel prognostic model based on apoptosis-related genes

Abstract

Background Dysregulation of the balance between proliferation and apoptosis is the basis in human hepatocarcinogenesis. There is a possible association of apoptosis dysregulation with poor prognosis in many malignant tumors, such as hepatocellular carcinoma (HCC). However, the prognostic effect of Apoptosis-related genes (ARGs) on HCC is still unclear. Methods A total of 161 ARGs expression levels were analyzed based on The Cancer Genome Atlas (TCGA) database(https://cancergenome.nih.gov/) to screen for differentially expressed ARGs. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to determine the underlying molecular mechanisms of screened ARGs in HCC. ARGs prognostic values were identified using Cox regression to subsequently establish a prognostic risk model and scoring in patients. Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curves were plotted to determine the prognostic value in the model. Results Compared to normal specimens, 43 highly upregulated and 8 downregulated ARGs respectively and their normal counterparts in HCC specimens were screened. KEGG analysis demonstrated pathways correlated with these 51 genes which included MAPK, P53, TNF, PI3K-Akt signaling pathways. With Cox regression, 5 prognostic correlated with ARGs (PPP2R5B, SQSTM1, TOP2A, BMF, and LGALS3) were obtained to develop the prognosis model. According to the median of risk scores, patients were categorized into high-risk and low-risk groups. Patients in low-risk groups had a significantly higher two-year or five-year survival probability (p < 0.0001). The risk model had better potency than other clinical characteristics, with the area under the ROC curve (AUC = 0.741). Prognosis of HCC patients was established from a plotted nomogram. Conclusion This present study established a novel prognostic risk model for predicting HCC according to the expression of ARGs. The present advancement can potentially contribute to prediction prognosis and individualized treatment of HCC patients.