Genetic variants in the Hedgehog signaling pathway genes are associated with gastric cancer risk in a Chinese Han population
Yujuan Zhang1
Kai Lu1
Xu Wu2
Hanting Liu1
Junyi Xin1
Xiaowei Wang1
Weida Gong3
Qinghong Zhao4
Meilin Wang5
Haiyan Chu1
Mulong Du6
Guoquan Tao2
Zhengdong Zhang5
1.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,China2.Department of General Surgery,the Affiliated Huai'an No.l People's Hospital of Nanjing Medical University,Huai'an,Jiangsu 223300,China3.Department of General Surgery,Yixing People's Hospital,Yixing,Jiangsu 214200,China4.Department of General Surgery,the Second Affiliated Hospital of Nanjing Medical University,Nanjing,Jiangsu 210011,China5.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;Department of Environmental Genomics,Center for Global Health,School of Public Health,Nanjing Medical University,Nanjing,Jiangsu 211166,China6.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 Biostatistics,Center for Global Health,School of Public Health,Nanjing Medical University,Nanjing 211166,China
摘要：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 KIF27 was associated with higher gastric cancer risk,especially in the young and male subgroups.The expression of KIF27 in gastric cancer tissues was higher than that in normal tissues,leading to poor survival in gastric cancer patients.Besides,KIF27 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.
机标关键词：
分类号：R735.2(消化系肿瘤)
论文发表日期：2022-01-30
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：10( 22-31 )
英文信息