Development and validation of a novel disulfidptosis-associated LncRNA model for risk stratification and targeted therapy guidance in gastric adenocarcinoma.

Abstract

Disulfidptosis, as a newly discovered form of cell programmed cell death in recent years, is driving the in-depth understanding of the tumor occurrence mechanism and the exploration of innovative therapeutic approaches. Although the regulatory role of long non-coding RNAs (lncRNAs) in cancer development is well-known, whether they are involved in the disulfidptosis process and their significance in the prognosis of gastric adenocarcinoma remain unclear. This study, using sequencing and clinical data from The Cancer Genome Atlas (TCGA) database, through least absolute shrinkage and selection operator (LASSO) and Cox regression analysis, has for the first time constructed a prognostic evaluation model containing eight disulfidptosis-related lncRNAs (DRlncRNAs). This model covers molecules such as LIMS1-AS1, LINC00460, and AL590681.1, and can clearly distinguish gastric adenocarcinoma patients into high-risk and low-risk groups based on the median risk score. The analysis showed that there were significant differences between the two groups of patients in terms of total survival, relevant signal pathway activity, tumor immune microenvironment characteristics, gene mutation load, drug sensitivity, etc. The prognosis of patients in the low-risk group is obviously better. Moreover, the study further verified through cell experiments, animal models and clinical samples that these 8 types of lncRNA are abnormally expressed in gastric adenocarcinoma, which directly affects the survival of cancer cells. This series of work not only provides a new independent biomarker combination for the prognosis of gastric adenocarcinoma, but also lays an important foundation for an in-depth understanding of the disulfidptosis regulation network and the development of targeted treatment strategies for this pathway.