Emerging evidence indicates that long noncoding RNAs (lncRNAs) are deeply involved in the biological processes driving gastric cancer (GC) progression and metastatic spread. Despite this, the prognostic value of tissue-based lncRNA expression for anticipating peritoneal recurrence in GC has not been thoroughly investigated. In the present study, we perform a comprehensive analysis of lncRNA expression patterns associated with peritoneal metastasis (PM) in GC and construct a composite lncRNA-derived risk score to stratify patients according to their likelihood of developing peritoneal recurrence after curative gastrectomy. Transcriptome-wide profiling of long noncoding RNAs was performed on matched peritoneal lesions, primary gastric tumors, and adjacent normal tissues obtained from 12 patients with gastric cancer in the Sun Yat-sen University Cancer Center (SYSUCC) discovery cohort. Candidate lncRNAs were subsequently screened through integrative analyses incorporating data from The Cancer Genome Atlas (TCGA) and an independent SYSUCC validation cohort. An lncRNA-based predictive score was developed using least absolute shrinkage and selection operator (LASSO) modeling combined with Cox regression–derived nomograms, and its performance was assessed by receiver operating characteristic (ROC) analysis. Finally, the functional involvement of selected lncRNAs in gastric cancer peritoneal metastasis was evaluated using wound-healing assays, Transwell migration and invasion assays, three-dimensional multicellular tumor spheroid invasion models, and in vivo peritoneal xenograft mouse models.Five key lncRNAs were identified and integrated into a peritoneal metastasis (PM) risk model for estimating peritoneal recurrence–free survival (pRFS). Building upon this model, we constructed a multidimensional nomogram incorporating the PM risk score alongside pathological T stage, pathological N stage, and tumor size, which demonstrated strong predictive performance for 5-year pRFS (AUC = 0.79, 95% CI: 0.71–0.88). Functional investigations further revealed that CASC15, one of the identified lncRNAs, enhanced gastric cancer cell migratory and invasive capacities in vitro and significantly promoted peritoneal dissemination in vivo, providing initial evidence for the involvement of lncRNAs in GC peritoneal metastasis. Mechanistic studies indicated that CASC15 drives epithelial–mesenchymal transition and metastatic behavior through activation of the JNK and p38 signaling pathways. In this work, we established a clinically applicable composite scoring system based on lncRNA expression to estimate the risk of peritoneal recurrence in patients with gastric cancer.
