Revealing the cuproptosis-lncRNA nexus in gastric cancer: A multicohort observational study

To establish a cuproptosis-related lncRNA signature and evaluate its prognostic value and potential immunological relevance in gastric cancer (GC). Transcriptomic data from the cancer genome atlas and gene expression omnibus were analyzed using Pearson correlation and least absolute shrinkage and selection operator Cox regression to construct the prognostic model. Model performance was assessed by Kaplan-Meier analysis, time-dependent receiver operating characteristic curves, and decision curve analysis. An mRNA-based RS score was further validated in Gene Expression Omnibus datasets and the IMvigor210 cohort. Expression of 2 key long noncoding RNAs (AC245041.1 and LINC01614) was confirmed by qRT-PCR in an independent GC cohort. A 25-lncRNA cuproptosis-related signature effectively stratified patients into high- and low-risk groups, with the high-risk group showing significantly poorer survival. The model outperformed conventional clinical variables. Functional enrichment suggested involvement of immune regulation and mitochondrial pathways related to cuproptosis, and the low-risk group displayed a more immunologically active profile. The RS score showed consistent predictive performance across external cohorts, and qRT-PCR validated the prognostic relevance of AC245041.1 and LINC01614. This cuproptosis-related lncRNA signature demonstrates potential as a prognostic indicator and may provide insights into immunotherapy relevance, offering a promising direction for personalized GC management.