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 with normal tissues, 43 highly upregulated and 8 downregulated 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 2-year or 5-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.

A pyroptosis-related gene signature predicts prognosis and immune microenvironment in hepatocellular carcinoma

“…Inhibition of HIF1A-AS1, a long noncoding RNA (lncRNA) overexpressing in HCC tissues, could enhanced starvation-induced apoptosis in HCC cell [ 30 ]. A prognostic model involved apoptosis-related genes with impressive prognostic predictive power was also established in HCC [ 31 ]. Furthermore, numerous prognostic genes and prognostic signature for HCC have been reported by many studies [ 32 – 35 ] and further evaluated by some meta-analysis [ 36 , 37 ].…”

Breast Cancer Prognosis Prediction and Immune Pathway Molecular Analysis Based on Mitochondria-Related Genes

“…We filled this research gap by constructing a prognosis risk score model based on four mitochondria-related genes. Besides its role in BRCA, BMF is also an important prognostic marker for patients with other cancers, such as colon cancer [ 20 ] and hepatocellular carcinoma [ 21 ]. MRPL36 is a mitochondrial ribosomal protein that has not been studied in BRCA, but MRPL36 has been correlated with poor progression-free survival in ovarian cancer [ 22 ].…”

Outcomes of adolescent and young patients with hepatocellular carcinoma after curative liver resection: a retrospective study

“…It is reasonable to estimate that young HCC patients are likely to have genetic factors contributing to the onset of cancers. A recent study implied that apoptosis-related genes in HCC were associated with the patient’s prognosis [ 21 ]. Furthermore, tumor size, vascular invasion, tumor capsule formation, satellite nodules, TNM stage, and AFP were identified as the significant variables both for disease-free and overall survival, which were in line with the previous studies [ 22 – 25 ].…”