Significance of RNA Processing Factors in Prognosis and Treatment of Hepatocellular Carcinoma: Implications for Precision Medicine

Abstract

Hepatocellular carcinoma (HCC) is a malignant tumor with heterogenous nature and high mortality worldwide. RNA processing has been implicated in tumorigenesis, progression, and prognosis to develop early diagnosis and targeted therapy for cancer, including HCC. This study aimed to identify and validate a novel RNA processing gene signature for predicting HCC prognosis. Transcriptome and clinical data of HCC samples were obtained from Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), Gene Expression Omnibus databases, and RNA processing factors from the AmiGO database. The least absolute shrinkage and selection operator and multivariate Cox regression analysis were performed to examine prognostic gene signatures. Correlation analysis of prognostic models with clinical features and HallMark pathway-based Genomic Variation Analysis enrichment analysis were performed. We identified seven distinguished RNA processing factors to build the prognostic model for HCC patients. ROC curve analysis of the TCGA-HCC, ICGC-HCC, and GSE76427 cohorts determined the ability to predict prognosis through a sevengene-based model (AUC > 0.7). A nomogram to forecast the overall survival among HCC patients was established. In addition, 7 cell types (CD3+ cells, CD8+ T cells, macrophage/monocyte, monocyte, myeloid dendritic cells, neutrophils and cancer-associated fibroblast) significantly differed between the two risk groups. Furthermore, enrichment analysis showed significant enrichment in fatty acid metabolism, lipogenesis, pancreatic beta cells, and bile acid metabolism in the low-risk group, while in the high-risk group, DNA repair, protein secretion, and mitotic pathways were significantly enriched. Analyzing the Tumor Immune Dysfunction and Exclusion results demonstrated that immune checkpoint blockade therapy was poorly efficacious in the high-risk group. This study constructed and validated a novel prognostic signature related to RNA processing factors in HCC, improving therapeutic strategies for HCC. Building such prognostic signatures could pave the way for developing targeted therapy and precision medicine in HCC.