Shen Chao, Yan Yichao, Liang Bin, Shi Ji, Wu Yan, Ning Ning, Chen Lin, Madan Ankit, Li Wei
Department of Gastroenterological Surgery, Peking University International Hospital, Beijing, China.
Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, China.
J Gastrointest Oncol. 2025 Jun 30;16(3):811-822. doi: 10.21037/jgo-2025-219. Epub 2025 May 28.
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.
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.
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.
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.
胃癌（GC）是一个重大的健康风险因素，其5年生存率约为8%，预后较差。本研究利用癌症基因组图谱（TCGA）的数据，在胃癌背景下研究钙信号相关基因的功能。
从TCGA数据库中检索胃癌患者的RNA测序数据和临床特征数据。进行综合分析以确定预后基因，并发现这些基因与胃癌相关的钙信号通路之间存在显著相关性。
单变量Cox回归分析确定了829个预后基因，主要与钙信号通路、粘着斑、细胞外基质（ECM）-受体相互作用以及癌症相关通路有关，所有这些都可能显著影响胃癌。通过一致性聚类，基于与钙信号相关的基因，确定了两种不同的胃癌分子亚型[簇1（C1）和簇2（C2）]。值得注意的是，C2可能作为一种风险预后指标，潜在地反映临床症状的进展。对生物过程的基因本体（GO）分析表明，在高风险C1队列中，这些基因显著参与细胞-基质粘附、钙离子稳态和细胞-底物粘附。同样，京都基因与基因组百科全书分析表明，高风险C1组中差异表达基因在很大程度上与ECM-受体相互作用、粘着斑、血管平滑肌收缩、癌症相关蛋白聚糖和钙信号通路相关的途径有关。此外，两个与钙信号相关的胃癌组在免疫活性方面存在显著差异。最小绝对收缩和选择算子回归分析确定了10个与胃癌钙信号相关的基因（即， ， ， ， ， ， ， ， ， 和 ）。通过受试者工作特征曲线分析评估预后模型的准确性，1年时曲线下面积为0.639，3年时为0.707，5年时为0.674。
我们建立了一种与钙信号相关的创新特征，可作为胃癌可靠的预后指标。我们的发现可能为胃癌的诊断和治疗方法的改进铺平道路。
