Zhang Yujuan, Lu Kai, Wu Xu, Liu Hanting, Xin Junyi, Wang Xiaowei, Gong Weida, Zhao Qinghong, Wang Meilin, Chu Haiyan, Du Mulong, Tao Guoquan, Zhang Zhengdong
Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
J Biomed Res. 2021 Oct 29;36(1):22-31. doi: 10.7555/JBR.35.20210091.
The Hedgehog signaling pathway participates in the occurrence and progression of cancers including gastric cancer. We conducted this study to evaluate whether genetic variants in the Hedgehog signaling pathway genes would affect gastric cancer risk. Multi-marker Analysis of GenoMic Annotation (MAGMA) was used to investigate the aggregated genetic effects of single nucleotide polymorphisms (SNPs) assigned to candidate genes. The relationship between SNPs and gastric cancer risk was estimated by multivariate logistic regression analyses. Gene expression was calculated using databases obtained from The Cancer Genome Atlas (TCGA) and The Gene Expression Omnibus (GEO). Kaplan-Meier plotter was used to evaluate the association between gene expression with gastric cancer survival. Tumor Immune Estimation Resource 2.0 (TIMER 2.0) was applied to determine the correlation between selected gene expression and the immune cell infiltration degree. We identified that the G allele of rs2990912 in was associated with higher gastric cancer risk, especially in the young and male subgroups. The expression of in gastric cancer tissues was higher than that in normal tissues, leading to poor survival in gastric cancer patients. Besides, expression was related to immune cell infiltration and positively correlated with PD-L1 expression. Our findings highlight the key role of genetic variation in the Hedgehog signaling pathway genes in gastric cancer susceptibility, which may provide important insights into the diagnosis, prognosis, and treatment of gastric cancer.
刺猬信号通路参与包括胃癌在内的多种癌症的发生和发展。我们开展本研究以评估刺猬信号通路基因中的遗传变异是否会影响胃癌风险。基因组注释多标记分析（MAGMA）用于研究指定给候选基因的单核苷酸多态性（SNP）的聚集遗传效应。通过多变量逻辑回归分析估计SNP与胃癌风险之间的关系。使用从癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）获得的数据库计算基因表达。使用Kaplan-Meier绘图工具评估基因表达与胃癌生存率之间的关联。应用肿瘤免疫估计资源2.0（TIMER 2.0）确定所选基因表达与免疫细胞浸润程度之间的相关性。我们发现，[基因名称]中rs2990912的G等位基因与较高的胃癌风险相关，尤其是在年轻和男性亚组中。[基因名称]在胃癌组织中的表达高于正常组织，导致胃癌患者生存率较低。此外，[基因名称]表达与免疫细胞浸润相关，且与PD-L1表达呈正相关。我们的研究结果突出了刺猬信号通路基因中的遗传变异在胃癌易感性中的关键作用，这可能为胃癌的诊断、预后和治疗提供重要见解。
