Identification of a 14-lncRNA Signature and Construction of a Prognostic Nomogram Predicting Overall Survival of Gastric Cancer.

Increasing evidence suggests that aberrant long noncoding (lnc) RNA expression plays a vital role in gastric cancer (GC) initiation and progression. Thus, we aimed to develop a lncRNA-based risk signature and nomogram to predict overall survival (OS) for patients with GC. Our primary cohort was composed of 341 patients with clinical and lncRNA expression data in The Cancer Genome Atlas stomach adenocarcinoma (TCGA STAD), the internal validation cohort was composed of 172 randomly assigned patients, and the external validation cohort was composed of 300 patients from GSE62254 dataset. A risk signature and nomogram were developed for the primary cohort and validated on the validation cohorts. Furthermore, gene set enrichment analysis (GSEA) was used to investigate the pathway enrichment for the risk signature. The expression patterns of several lncRNAs were also investigated in clinical samples from 10 GC patients. We identified and validated a 14-lncRNA signature highly associated with the OS of patients with GC, which performed well on evaluation with C-index, area under the curve, and calibration curves. In addition, univariate and multivariate Cox regression analyses indicated that the lncRNA signature was an independent predictive factor for GC patients. Therefore, a nomogram incorporating lncRNA signature and clinical factors was constructed to predict OS for patients with GC in primary cohort that suggested powerful predictive values for survival in the TCGA cohort and the other two validation cohorts. In addition, GSEA indicated that the identified lncRNAs may regulate the autophagy pathway, affecting tumorigenesis and prognosis of patients with GC. Experimental validation demonstrated that the expression of lncRNAs showed the same trend both in our clinical samples and STAD dataset. These results suggest that both risk signature and nomogram were effective prognostic indicators for patients with GC.