Construction and validation of a prognostic model associated with chromatin remodeling in hepatocellular carcinoma

Abnormal chromatin remodeling figures prominently in the progression and treatment of malignancies. However, the prognostic significance of chromatin remodeling-related genes (CRRGs) in hepatocellular carcinoma (HCC) has not been extensively examined. Therefore, this study aimed to identify prognostic genes associated with chromatin remodeling in HCC and to determine their prognostic significance.

Differential expression analysis was conducted on The Cancer Genome Atlas-liver hepatocellular carcinoma (TCGA-LIHC) dataset to identify differentially expressed genes (DEGs). By overlapping DEGs with CRRGs and performing enrichment analysis, we identified chromatin remodeling-related DEGs (CRR-DEGs). Risk models were developed via least absolute shrinkage and selection operator (LASSO) and Cox regression analyses and were validated in International Cancer Genome Consortium Liver Cancer-RIKEN, Japan (ICGC-LIRI-JP) dataset. Independent prognostic factors were screened out according to risk scores and clinical indicators, and a nomogram was created. Additional analysis included survival, expression, mutation, enrichment, and regulatory network predictions.

Eighteen CRR-DEGs were identified through the intersection of DEGs and CRRGs, all of which were found to be enriched in adenosine triphosphate (ATP)-dependent chromatin remodeling pathways, and eight of which were found to be specifically enriched in HCC. Four prognostic genes (ACTR5, NFRKB, RBBP7, and RUVBL1) were selected to construct a risk model via LASSO and univariate Cox regression analyses, which was validated in the ICGC-LIRI-JP dataset. Calibration curves and receiver operating characteristic (ROC) curve analysis indicated the superior accuracy of the nomogram for predicting HCC with chromatin remodeling. Enrichment analysis linked the prognostic genes to pathways such as DNA replication, spliceosome, and cell cycle.

Four prognostic genes associated with chromatin remodeling in HCC were identified, and a prognostic model for HCC was established, offering valuable insights for the development of HCC treatment strategies.