Research Paper Volume 15, Issue 11 pp 4906—4925
A spliceosome-associated gene signature aids in predicting prognosis and tumor microenvironment of hepatocellular carcinoma
- 1 Department of Hepatobiliary and Pancreatic Surgery, Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, Shiyan 442000, Hubei, China
- 2 Department of Hepatobiliary Medicine, The Third People’s Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou 350108, Fujian, China
Received: March 11, 2023 Accepted: May 17, 2023 Published: June 10, 2023
https://doi.org/10.18632/aging.204765How to Cite
Copyright: © 2023 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Splicing alterations have been shown to be key tumorigenesis drivers. In this study, we identified a novel spliceosome-related genes (SRGs) signature to predict the overall survival (OS) of patients with hepatocellular carcinoma (HCC). A total of 25 SRGs were identified from the GSE14520 dataset (training set). Univariate and least absolute shrinkage and selection operator (LASSO) regression analyses were utilized to construct the signature using genes with predictive significance. We then constructed a risk model using six SRGs (BUB3, IGF2BP3, RBM3, ILF3, ZC3H13, and CCT3). The reliability and predictive power of the gene signature were validated in two validation sets (TCGA and GSE76427 dataset). Patients in training and validation sets were divided into high and low-risk groups based on the gene signature. Patients in high-risk groups exhibited a poorer OS than in low-risk groups both in the training set and two validation sets. Next, risk score, BCLC staging, TNM staging, and multinodular were combined in a nomogram for OS prediction, and the decision curve analysis (DCA) curve exhibited the excellent prediction performance of the nomogram. The functional enrichment analyses demonstrated high-risk score patients were closely related to multiple oncology characteristics and invasive-related pathways, such as Cell cycle, DNA replication, and Spliceosome. Different compositions of the tumor microenvironment and immunocyte infiltration ratio might contribute to the prognostic difference between high and low-risk score groups. In conclusion, a spliceosome-related six-gene signature exhibited good performance for predicting the OS of patients with HCC, which may aid in clinical decision-making for individual treatment.
Abbreviations
HCC: hepatocellular carcinoma; SRGs: Spliceosome-related genes; LASSO: least absolute shrinkage and selection operator; DCA: decision curve analysis; IHC: Immunohistochemistry; OS: Overall survival; AFP: Alpha-fetoprotein; GO: the Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; GSEA: Gene Set Enrichment Analyses; ssGSEA: single sample GSEA; ROC: Receiver operating characteristic; PFS: progression-free survival; PPI: protein-protein interaction; FDR: false discovery rate; AUC: Area under the curve; TNM: tumor-node-metastasis; aHR: adjusted Hazard ratio; CI: Confidence interval; BUB3: budding uninhibited by benzimidazole 3; IGF2BP3: insulin-like growth factor 2 mRNA binding protein 3; RBM3: RNA binding motif protein 3; ILF3: interleukin enhancer binding factor 3; ZC3H13: zinc finger CCCH-type containing 13; CCT3: chaperonin containing TCP1subunit 3.