Genes associated with calcium signaling have promising diagnostic potential for gastric cancer.

[BACKGROUND] Gastric cancer (GC) represents a considerable health risk, characterized by a poor 5-year survival rate of approximately 8%. Using data from The Cancer Genome Atlas (TCGA), this study investigated the function of calcium signaling-related genes in the context of GC.

[METHODS] The RNA sequencing data and clinical characteristic data of GC patients were retrieved from TCGA database. A comprehensive analysis was conducted to identify the prognostic genes, and a significant correlation was found between these genes and the calcium signaling pathways related to GC.

[RESULTS] The univariate Cox regression analysis identified 829 prognostic genes, primarily related to the calcium signaling pathway, focal adhesion, extracellular matrix (ECM)-receptor interaction, and cancer-associated pathways, all of which may significantly affect GC. Through consensus clustering, two distinct molecular subtypes of GC were identified [Cluster 1 (C1) and Cluster 2 (C2)] based on the genes associated with calcium signaling. Notably, C2 may serve as a prognostic indicator of risk, potentially reflecting the progression of clinical symptoms. The Gene Ontology (GO) analysis of biological processes revealed that these genes were significantly involved in cell-matrix adhesion, calcium ion homeostasis, and cell-substrate adhesion in the high-risk C1 cohort. Similarly, the Kyoto Encyclopedia of Genes and Genomes analysis indicated that the differentially expressed genes were largely associated with the pathways related to ECM-receptor interactions, focal adhesion, vascular smooth muscle contraction, cancer-related proteoglycans, and calcium signaling pathways in the high-risk C1 group. Further, there were significant differences in the immune activity of the two calcium signaling-related GC groups. The least absolute shrinkage and selection operator regression analysis identified 10 genes associated with calcium signaling in GC (i.e., , , , , , , , , , and ). The accuracy of the prognostic model was assessed by a receiver operating characteristic curve analysis, yielding areas under the curve of 0.639 for 1 year, 0.707 for three years, and 0.674 for 5 years.

[CONCLUSIONS] We established an innovative signature associated with calcium signaling that serves as a reliable prognostic indicator for GC. Our findings may pave the way for enhanced diagnostic and therapeutic approaches in the context of GC.