Construction and Validation of a Reliable Disulfidptosis-Related LncRNAs Signature of the Subtype, Prognostic, and Immune Landscape in Colon Cancer

Abstract

Disulfidptosis, a novel form of regulated cell death (RCD) associated with metabolism, represents a promising intervention target in cancer therapy. While abnormal lncRNA expression is associated with colon cancer development, the prognostic potential and biological characteristics of disulfidptosis-related lncRNAs (DRLs) remain unclear. Consequently, the research aimed to discover a novel indication of DRLs with significant prognostic implications, and to investigate their possible molecular role in the advancement of colon cancer. Here, we acquired RNA-seq data, pertinent clinical data, and genomic mutations of colon adenocarcinoma (COAD) from the TCGA database, and then DRLs were determined through Pearson correlation analysis. A total of 434 COAD patients were divided in to three subgroups through clustering analysis based on DRLs. By utilizing univariate Cox regression, the least absolute shrinkage and selection operator (LASSO) algorithm, and multivariate Cox regression analysis, we ultimately created a prognostic model consisting of four DRLs (AC007728.3, AP003555.1, ATP2B1.AS1, and NSMCE1.DT), and an external database was used to validate the prognostic features of the risk model. According to the Kaplan–Meier curve analysis, patients in the low-risk group exhibited a considerably superior survival time in comparison to those in the high-risk group. Enrichment analysis revealed a significant association between metabolic processes and the genes that were differentially expressed in the high- and low-risk groups. Additionally, significant differences in the tumor immune microenvironment landscape were observed, specifically pertaining to immune cells, function, and checkpoints. High-risk patients exhibited a low likelihood of immune evasion, as indicated by the Tumor Immune Dysfunction and Exclusion (TIDE) analysis. Patients who exhibit both a high risk and high Tumor Mutational Burden (TMB) experience the least amount of time for survival, whereas those belonging to the low-risk and low-TMB category demonstrate the most favorable prognosis. In addition, the risk groups determined by the 4-DRLs signature displayed distinct drug sensitivities. Finally, we confirmed the levels of expression for four DRLs through rt-qPCR in both tissue samples from colon cancer patients and cell lines. Taken together, the first 4-DRLs-based signature we proposed may serve for a hopeful instrument for forecasting the prognosis, immune landscape, and therapeutic responses in colon cancer patients, thereby facilitating optimal clinical decision-making.

PPARγ Antagonists Exhibit Antitumor Effects by Regulating Ferroptosis and Disulfidptosis

“…Although research on disulfidptosis is currently limited, some researchers have found that genes associated with disulfidptosis are linked to various immune cells. It holds significant potential in influencing the tumor microenvironment [38,39]. Our data confirmed that the inhibition of PPARγ in OSCC simultaneously induces ferroptosis and disulfidptosis.…”

An anoikis-related lncRNA signature may predict the prognosis, immune infiltration, and drug sensitivity in esophageal cancer

“…The construction of predictive models that incorporate molecular signatures has emerged as a potent approach to enhance prognostic assessment in various cancers [ 14 ]. In our study, we established a novel risk score model hinging on a panel of ten prognostic anoikis-related lncRNAs.…”

ALMS1-IT1: A Key Player in the Novel Disulfidptosis-Related LncRNA Prognostic Signature for Head and Neck Squamous Cell Carcinoma

“…Although a number of disulfidptosis-related lncRNA prognostic signatures can predict the survival of cancer patients [ 35 , 36 , 37 ], the involvement of individual lncRNAs in disulfidptosis remains to be experimentally validated. This study is the first to identify an individual lncRNA that can be regarded as a regulatory factor in disulfidptosis.…”