P53相关基因IL1A和F2R在胃癌中的表达及功能分析
Expression and Function of P53-Related Genes IL1A and F2R in Gastric Cancer
王志远 1刘文博 1苑新宇 1张卓奇 2霍炳杰 1耿建磊 3王冰雨 1王盈盈 1李勇 1檀碧波1
作者信息
- 1. 河北医科大学第四医院,河北石家庄 050011
- 2. 上海市第六人民医院金山分院,上海 201599
- 3. 河北省儿童医院,河北石家庄 050031
- 折叠
摘要
[目的]分析胃癌中P53相关基因白细胞介素1α(interleukin 1α,IL1A)、凝血因子Ⅱ凝血酶受体(coagulation factor Ⅱ thrombin receptor,F2R)的表达及功能,寻找胃癌新的生物标志物.[方法]从癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库获取胃癌的RNA-seq表达数据和临床数据,包含375个胃癌组织和32个正常组织,从MSigDB获取P53相关基因集合.使用Fold Change和Wilcoxon检验筛选差异表达基因并对其进行富集分析、生存分析;计算P53相关基因在胃癌样本中的突变信息.选取临床中20例胃癌及癌旁组织样本,运用实时荧光定量PCR(RT-qPCR)验证IL1A和F2R在胃癌及癌旁组织中的表达水平.[结果]TCGA数据库中,IL1A、F2R在胃癌样本中表达水平分别为13.31±2.07和18.69±0.92,均高于癌旁组织(P=0.003,P＜0.001).生存分析显示IL1A、F2R高表达胃癌患者的5年生存率更差(P=0.021,P=0.028),IL1A、F2R高表达是胃癌患者生存的危险因素.富集分析表明IL1A、F2R与细胞活化、炎症反应等相关.P53相关基因在胃癌样本中高频突变,有突变显著共出现(P＜0.01).临床病例中,RT-qPCR验证结果表明IL1A、F2R在胃癌组织中的表达水平均高于癌旁组织(P均＜0.001).[结论]IL1A、F2R在胃癌发生及进展中发挥作用,是潜在的胃癌生物标志物.
Abstract
[Objective]To analyze the expression and function of P53-related genes in gastric cancer.[Methods]RNA-seq expression data and clinical data of gastric cancer were obtained from the Cancer Genome Atlas(TCGA)database,including 375 gastric cancer tissues and 32 normal tissues;and P53-related gene sets were obtained from MSigDB.Fold change and Wilcox-on were used to screen differentially expressed genes,and their enrichment analysis and survival analysis were performed.The mutation information of P53-related genes in gastric cancer samples was calculated.The expression levels of interleukin 1α(IL1A)and coagulation factor Ⅱ thrombin receptor(F2R)in gastric cancer and adjacent tissues were determined by quantitative real-time PCR(RT-qPCR).[Results]In the TCGA database,the expression levels of IL1A and F2R in gastric cancer samples were 13.31±2.07 and 18.69±0.92,which were higher than those in adja-cent tissues(P=0.003,P＜0.001).Survival analysis showed that the 5-year survival rate of patients with high expression of IL1A and F2R was worse(P=0.021,P=0.028),the high expression of IL1A and F2R was the risk factor for survival of gastric cancer patients.Enrichment analysis showed that IL1A and F2R were related to cell activation and inflammatory response.P53-related genes were frequently mutated in gastric cancer samples,with significant co-mutation(P＜0.01).In clinical cases,the expression levels of IL1A and F2R in gastric cancer tissues were higher than those in adjacent tissues(all P＜0.001).[Conclusion]IL1A and F2R play a role in gastric car-cinogenesis and may be potential gastric cancer biomarkers.
关键词
胃肿瘤/P53/白细胞介素1α/凝血因子Ⅱ凝血酶受体/生物信息学分析/生物标志物Key words
gastric neoplasms/P53/IL1A/F2R/bioinformatics analysis/biomarkers引用本文复制引用
基金项目
河北省科技厅重点研发计划(22377701D)
河北医科大学"十四五"临床医学创新研究团队支持计划(2022LCTD-A13)
河北省2022年政府资助省级医学优秀人才项目(冀财预复[2022]180号)
河北省2023年度医学科学研究课题(20230123)
2022年度河北省医学适用技术跟踪项目(GZ2022044)
出版年
2024
NETL
NSTL
万方数据