Comprehensive Analysis of Disulfidptosis-Related LncRNAs in Molecular Classification, Immune Microenvironment Characterization and Prognosis of Gastric Cancer.

Abstract

Disulfidptosis is a novel form of programmed cell death that unveils promising avenues for the exploration of tumor treatment modalities. Gastric cancer (GC) is a malignant tumor characterized by high incidence and mortality rate. However, there has been no systematic study of disulfidptosis-related long noncoding RNAs (DRLs) signature in GC patients. The lncRNA expression profiles containing 412 GC samples were acquired from the Cancer Genome Atlas (TCGA) database. Differential expression analysis was performed alongside Pearson correlation analysis to identify DRLs. Prognostically significant DRLs were further screened using univariate COX regression analysis. Subsequently, LASSO regression and multifactorial COX regression analyses were employed to establish a risk signature composed of DRLs that exhibit independent prognostic significance. The predictive value of this risk signature was further validated in a test cohort. The ESTIMATE, CIBERSORT and ssGSEA methodologies were utilized to investigate the tumor immune microenvironment of GC populations with different DRLs profiles. Finally, the correlation between DRLs and various GC drug responses was explored. We established a prognostic signature comprising 12 disulfidptosis-related lncRNAs (AC110491.1, AL355574.1, RHPN1-AS1, AOAH-IT1, AP001065.3, MEF2C-AS1, AC016394.2, LINC00705, LINC01952, PART1, TNFRSF10A-AS1, LINC01537). The Kaplan-Meier survival analysis revealed that patients in the high-risk group exhibited a poor prognosis. Both univariate and multivariate COX regression models demonstrated that the DRLs signature was an independent prognostic indicator in GC patients. Furthermore, the signature exhibited accurate predictions of survival at 1-, 3- and 5- years with the area under the curve (AUC) values of 0.708, 0.689 and 0.854, respectively. In addition, we also observed significant associations between the DRLs signature and various clinical variables, distinct immune landscape and drug sensitivity profiles in GC patients. The low-risk group patients may be more likely to benefit from immunotherapy and chemotherapy. Our study investigated the role and potential clinical implications of DRLs in GC. The risk model constructed by DRLs demonstrated high accuracy in predicting the survival outcomes of GC and improving the treatment efficacy for GC patients.