Research Paper Volume 16, Issue 1 pp 267—284
A novel disulfidptosis-related lncRNAs signature for predicting survival and immune response in hepatocellular carcinoma
- 1 The First Central Clinical School, Tianjin Medical University, Tianjin, China
- 2 Department of Liver Transplantation, Tianjin First Central Hospital, Tianjin Medical University, Key Laboratory of Transplantation, Chinese Academy of Medical Sciences, Tianjin Key Laboratory for Organ Transplantation, Tianjin Key Laboratory of Molecular and Treatment of Liver Cancer, Tianjin, China
Received: June 26, 2023 Accepted: November 15, 2023 Published: January 4, 2024
https://doi.org/10.18632/aging.205367How to Cite
Copyright: © 2024 Guo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
The accumulation of intracellular disulfides induces a novel and unique form of metabolic-related cell death known as disulfidptosis. A previous study revealed the prognostic value of a risk model of disulfidptosis-related genes in hepatocellular carcinoma (HCC). However, to date, no studies have investigated the relationship between disulfidptosis-related long non-coding RNAs (DRLs) and HCC. In this study, we collected and analyzed RNA sequencing data from 370 HCC samples to explore the DRLs in the tumorigenesis and development of HCC. By employing Lasso Cox regression and multivariate Cox regression analyses, we identified five prognostic DRLs, which were used to construct a prognostic signature. The signature was subsequently validated using receiver operating characteristic (ROC) curves, Kaplan-Meier analysis, Cox regression analyses, nomograms, and calibration curves. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were performed, revealing that the DRLs signature was associated with HCC and several cancer-related pathways. Furthermore, the DRLs signature showed correlations with the infiltration of M0 and M1 macrophages, immune-related functions, and multiple immune checkpoints, including PDCD1, LAG3, CTLA4, TIGIT, CD47, and others. Analysis using the tumor immune dysfunction and exclusion (TIDE) approach demonstrated that the DRLs signature could predict the response to immunotherapy. Finally, we screened potential chemotherapy drugs that could sensitize HCC. In conclusion, our novel DRLs signature provides valuable insights into predicting patient survival and immunotherapy responses.
Abbreviations
BP: biological processes; CC: cellular composition; DEGs: differentially expressed genes; DRGs: disulfidptosis-related genes; DRLs: disulfidptosis-related lncRNAs; GO: gene ontology; GSEA: the gene set enrichment analysis; HBV: hepatitis B virus; HCC: hepatocellular carcinoma; HCV: hepatitis C virus; HPA: Human Protein Atlas; ICIs: immune checkpoint inhibitors; KEGG: Kyoto Encyclopedia of Genes and Genomes; LncRNAs: long noncoding RNAs; MF: molecular function; NADPH: nicotinamide adenine dinucleotide phosphate; NAFATc1: nuclear factor of activated T-cells 1; OS: overall survival; PCA: principal component analysis; PFS: progression free survival; ROC: receiver operating characteristic; SLC7A11: solute carrier family 7 member 11; TCGA: The Cancer Genome Atlas; TIDE: tumor immune dysfunction and exclusion; TMB: tumor mutation burden; TME: tumor immune microenvironment; TXNRD1: thioredoxin reductase 1.