Constructing and investigating a disulfidptosis-associated LncRNA signature for prognostic prediction in gastric cancer

BACKGROUND: Gastric cancer (GC) prognosis remains poor, necessitating reliable biomarkers. Disulfidptosis represents a promising therapeutic frontier. This study aimed to construct a prognostic model based on disulfidptosis-related LncRNAs (DRLs) and investigate their function. METHODS: DRLs were screened from TCGA-STAD using Pearson correlation and LASSO-COX regression to build a prognostic signature. Its accuracy was evaluated via Kaplan-Meier analysis, time-dependent ROC curves, and decision curve analysis. A key DRL was functionally validated in vitro and in vivo. RESULTS: We established a six-DRL signature (AC090809.1, CYP4A22-AS1, AL356417.2, Z94721.2, FP325313.3, ERICH3-AS1) that effectively stratified patients into risk groups with distinct survival (P < 0.05). The risk score was an independent prognostic factor, with robust predictive AUCs for 1-, 2-, and 3-year survival. AL356417.2 was upregulated in GC and linked to poor outcome. Its knockdown inhibited cell viability, induced F-actin depolymerization, increased cystine uptake, and suppressed tumor growth in mice. CONCLUSION: We developed a novel DRL-based prognostic model and identified AL356417.2 as a functional regulator suppressing disulfidptosis, providing mechanistic insights and a potential therapeutic target for GC.