Background:Findings on the association of genetic factors and colorectal cancer(CRC)survival are limited and inconsistent,and revealing the mechanism underlying their prognostic roles is of great importance.This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism. Methods:We first systematically performed expression quantitative trait locus(eQTL)analysis using The Cancer Genome Atlas(TCGA)dataset.Then,the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets(TCGA and GSE39582 dataset from the Gene Expression Omnibus database).The seven most potentially functional eQTL single nucleotide polymorphisms(SNPs)associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data.The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments. Results:The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1(ERAP1)was significantly associated with the prognosis of CRC(additive model,hazard ratio[HR]:1.43,95％confidence interval[CI]:1.08-1.88,P=0.012).The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3(TCF3)and subsequently reduce the expression of ERAP1.The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes. Conclusion:The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1.
Danyi Zou;Chaoqun Huang;Ying Zhu;Xiaoping Miao;Yongchang Wei;Xiaojun Yang;Jianbo Tian;Yimin Cai;Meng Jin;Ming Zhang;Yizhuo Liu;Shuoni Chen;Shuhui Yang;Heng Zhang;Xu Zhu
Department of Clinical Laboratory,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430022,China||Department of Epidemiology and Biostatistics,School of Public Health,TaiKang Center for Life and Medical Sciences,Wuhan University,Wuhan,Hubei 430071,China||Department of Gastrointestinal Oncology,Zhongnan Hospital of Wuhan University,Wuhan,Hubei 430071,ChinaDepartment of Gastrointestinal Surgery,Zhongnan Hospital of Wuhan University,Wuhan University,Wuhan,Hubei 430071,ChinaDepartment of Epidemiology and Biostatistics,School of Public Health,TaiKang Center for Life and Medical Sciences,Wuhan University,Wuhan,Hubei 430071,China||Department of Gastrointestinal Oncology,Zhongnan Hospital of Wuhan University,Wuhan,Hubei 430071,ChinaDepartment of Epidemiology and Biostatistics,School of Public Health,TaiKang Center for Life and Medical Sciences,Wuhan University,Wuhan,Hubei 430071,China||Department of Gastrointestinal Oncology,Zhongnan Hospital of Wuhan University,Wuhan,Hubei 430071,China||Department of Epidemiology and Biostatistics,School of Public Health,Tongji Medical College,Huazhong University of Sciences and Technology,Wuhan,Hubei 430030,China||Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine,Nanjing Medical University,Nanjing,Jiangsu 211166,ChinaDepartment of Gastrointestinal Oncology,Zhongnan Hospital of Wuhan University,Wuhan,Hubei 430071,ChinaDepartment of Oncology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430030,ChinaDepartment of Gastrointestinal Surgery,Renmin Hospital of Wuhan University,Wuhan,Hubei 430071,China
Colorectal cancer;Prognosis;Genetic variation;Quantitative trait loci;ERAP1;TCF3;rs71630754;Single nucleo-tide polymorphisms
《中华医学杂志（英文版）》 2024 (004)
431-440 / 10
This study was supported by grants from the National Natural Science Foundation of China(Nos.82273713 and 82103929),the Young Elite Scientists Sponsorship Program by CAST(No.2022QNRC001),the Funda-mental Research Funds for the Central Universities(No.WHU:2042022kf1205),the Knowledge Innovation Pro-gram of Wuhan(No.whkxjsj011),the Distinguished Young Scholars of China(No.81925032),the Key Pro-gram of National Natural Science Foundation of China(No.82130098),the Hubei Provincial Natural Science Foundation of China(No.2019CFA009),the Youth Pro-gram of National Natural Science Foundation of China(No.82003547)and the Fundamental Research Funds for the Central Universities(No.WHU:2042022kf 1031).
10.1097/CM9.0000000000002845
评论