Prognostic value of disulfidptosis-associated genes in gastric cancer: a comprehensive analysis.

Objective: Disulfidptosis is a newly identified type of nonapoptotic programmed cell death related to mechanisms such as ferroptosis, cuproptosis, pyroptosis, and necrotic apoptosis. This study explores the role of disulfidptosis-related long non-coding RNAs (DRLs) in gastric cancer and their potential as prognostic biomarkers.

Method: We developed a prognostic model using DRL scores to classify patients based on disulfidptosis activity. We evaluated these scores for correlations with drug sensitivity, tumor microenvironment (TME) features, tumor mutational burden (TMB), and prognosis. Potential disulfidptosis-related signaling pathways were screened, identifying FRMD6-AS as a promising therapeutic target. FRMD6-AS expression was further validated using real-time fluorescent quantitative PCR (qRT-PCR).

Results: The DRL-based prognostic model, established through univariate and multivariate Cox regression and LASSO regression analyses, outperformed traditional models in predicting prognosis. We divided samples into high-risk and low-risk groups based on DRL scores, finding that the low-risk group had a significantly higher survival rate (P < 0.05). A high-precision prediction model incorporating DRL scores, age, sex, grade, and stage showed strong predictive value and consistency with actual outcomes. High DRL scores correlated with higher TME scores and lower TMB. Key signaling axes identified were AC129507.1/(FLNA, TLN1)/FOCAL ADHESION and AC107021.2/MYH10/(TIGHT JUNCTION, VIRAL MYOCARDITIS, REGULATION OF ACTIN CYTOSKELETON). Potentially effective drugs, including BMS-754807, dabrafenib, and JQ1, were identified. FRMD6-AS emerged as a potential target for gastric cancer treatment.

Conclusions: This study developed a novel prognostic model for gastric cancer using DRLs, identifying two key signaling axes related to prognosis. JQ1 may be an effective treatment, and FRMD6-AS could be a promising therapeutic target.