A prognostic model for hepatocellular carcinoma based on apoptosis-related genes

Abstract

Background: Dysregulation of the balance between proliferation and apoptosis is the basis for human hepatocarcinogenesis. In many malignant tumors, such as hepatocellular carcinoma (HCC), there is a correlation between apoptotic dysregulation and poor prognosis. However, the prognostic values of apoptosis-related genes (ARGs) in HCC have not been elucidated. Methods: To screen for differentially expressed ARGs, the expression levels of 161 ARGs from The Cancer Genome Atlas (TCGA) database(https://cancergenome.nih.gov/) were analyzed. Gene Ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to evaluate the underlying molecular mechanisms of differentially expressed ARGs in HCC. The prognostic values of ARGs were established using Cox regression, and subsequently, a prognostic risk model for scoring patients was developed. Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curves were plotted to determine the prognostic value of the model. Results: Compared to normal tissues, 43 highly up-regulated and 8 down-regulated ARGs in HCC tissues were screened. GO analysis results revealed that these 51 genes are indeed related to the apoptosis function. KEGG analysis revealed that these 51 genes were correlated with MAPK, P53, TNF, and PI3K-AKT signaling pathways, while Cox regression revealed that 5 ARGs (PPP2R5B, SQSTM1, TOP2A, BMF, and LGALS3) were associated with prognosis and were, therefore, obtained to develop the prognostic model. Based on the median risk scores, patients were categorized into high-risk and low-risk groups. Patients in the low-risk groups exhibited significantly elevated two-year or five-year survival probabilities (p < 0.0001). The risk model had a better clinical potency than the other clinical characteristics, with the area under the ROC curve (AUC = 0.741). The prognosis of HCC patients was established from a plotted nomogram. Conclusion: Based on the differential expression of ARGs, we established a novel risk model for predicting HCC prognosis. This model can also be used to inform the individualized treatment of HCC patients.

Secondarily estimated cure fraction and five-year recurrence-free conditional survival probabilities among patients undergoing surgical resection for hepatocellular carcinoma presenting with minor gross vascular invasion

“…Epidemiological studies show that both the incidence rate and related mortality of HCC increased during the last decade [2]. Recently, many studies have been performed to elucidate molecular mechanisms of HCC, and to identify an effective genetic biomarkers for individualized treatment [3][4][5][6]. Curative treatment options, such as surgical resection (SR), liver transplantation (LT), and locoregional therapies, provide relatively favorable outcomes for patients fulfilling their own selective criteria [7][8][9].…”