Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Guangxi Clinical Research Center for Colorectal Cancer, He Di Road 71, Nanning, 530021, Guangxi Autonomous Region, People's Republic of China.
Department of General Surgery, The People's Hospital of Binyang County, Nanning, 530405, Guangxi Zhuang Autonomous Region, People's Republic of China.
Sci Rep. 2021 Dec 8;11(1):23674. doi: 10.1038/s41598-021-03086-1.
While cadherin (CDH) genes are aberrantly expressed in cancers, the functions of CDH genes in gastric cancer (GC) remain poorly understood. The clinical significance and molecular mechanisms of CDH genes in GC were assessed in this study. Data from a total of 1226 GC patients included in The Cancer Genome Atlas (TCGA) and Kaplan-Meier plotter database were used to independently explore the value of CDH genes in clinical application. The TCGA RNA sequencing dataset was used to explore the molecular mechanisms of CDH genes in GC. Using enrichment analysis tools, CDH genes were found to be related to cell adhesion and calcium ion binding in function. In TCGA cohort, 12 genes were found to be differentially expressed between GC para-carcinoma and tumor tissue. By analyzing GC patients in two independent cohorts, we identified and verified that CDH2, CDH6, CDH7 and CDH10 were significantly associated with a poor GC prognosis. In addition, CDH2 and CDH6 were used to construct a GC risk score signature that can significantly improve the accuracy of predicting the 5-year survival of GC patients. The GSEA approach was used to explore the functional mechanisms of the four prognostic CDH genes and their associated risk scores. It was found that these genes may be involved in multiple classic cancer-related signaling pathways, such as the Wnt and phosphoinositide 3-kinase signaling pathways in GC. In the subsequent CMap analysis, three small molecule compounds (anisomycin, nystatin and bumetanide) that may be the target molecules that determine the risk score in GC, were initially screened. In conclusion, our current study suggests that four CDH genes can be used as potential biomarkers for GC prognosis. In addition, a prognostic signature based on the CDH2 and CDH6 genes was constructed, and their potential functional mechanisms and drug interactions explored.
虽然钙黏蛋白（CDH）基因在癌症中异常表达，但它们在胃癌（GC）中的功能仍知之甚少。本研究评估了 CDH 基因在 GC 中的临床意义和分子机制。使用来自癌症基因组图谱（TCGA）和 Kaplan-Meier plotter 数据库的总共 1226 名 GC 患者的数据，独立探索 CDH 基因在临床应用中的价值。使用 TCGA RNA 测序数据集探索 GC 中 CDH 基因的分子机制。使用富集分析工具，发现 CDH 基因在功能上与细胞黏附和钙离子结合有关。在 TCGA 队列中，发现 12 个基因在 GC 癌旁组织和肿瘤组织之间表达差异。通过分析两个独立队列的 GC 患者，我们鉴定并验证了 CDH2、CDH6、CDH7 和 CDH10 与 GC 预后不良显著相关。此外，CDH2 和 CDH6 被用于构建 GC 风险评分标志物，可显著提高预测 GC 患者 5 年生存率的准确性。使用 GSEA 方法探索四个预后 CDH 基因及其相关风险评分的功能机制。发现这些基因可能参与 GC 中的多个经典癌症相关信号通路，如 Wnt 和磷酸肌醇 3-激酶信号通路。在随后的 CMap 分析中，初步筛选了三种可能是 GC 中决定风险评分的靶分子的小分子化合物（放线菌酮、制霉菌素和布美他尼）。总之，本研究表明，四个 CDH 基因可作为 GC 预后的潜在生物标志物。此外，构建了基于 CDH2 和 CDH6 基因的预后标志物，并探索了它们的潜在功能机制和药物相互作用。
