PDHA1在乳腺癌中遗传变异、免疫浸润及ceRNA网络构建的综合分析  

Integrative Analysis of Genetic Variation,Immune Infiltration and ceRNA Network Construction of PDHA1 in Breast Cancer

作　　者：郭妙兰 易嘉宁 杨秋怡 范培芝[1] 喻洁[1] 曾杰[1] GUO Miaolan;YI Jianing;YANG Qiuyi;FAN Peizhi;YU Jie;ZENG Jie(The First Affiliated Hospital of Hunan Normal University/Hunan Provincial People's Hospital,Changsha 410005)

机构地区：[1]湖南师范大学附属第一医院/湖南省人民医院,长沙410005

出　　处：《湖南师范大学学报(医学版)》2024年第6期11-21,共11页Journal of Hunan Normal University(Medical Sciences)

基　　金：湖南省自然科学基金面上项目“山奈酚通过PLPP4介导的VEGFR2泛素化抑制三阴性乳腺癌进展转移及血管生成的机制研究”(2022JJ30335);湖南师范大学附属第一医院/湖南省人民医院博士基金资助项目“靶向PALB2-BRCA2结合的小分子增加乳腺癌细胞PARP抑制剂敏感性的作用和机制研究”(BSJJ202107)

摘　　要：目的:利用生物信息学方法和我院临床样本实验探究丙酮酸脱氢酶E1α亚单位(pyruvate dehydrogenase E1α subunit,PDHA1)在乳腺癌中表达和生物学作用。方法:挖掘TCGA和GTEx数据库,探讨PDHA1在乳腺癌和正常组织中的mRNA表达水平;收集我院临床样本进行免疫组化实验验证PDHA1蛋白的表达;在OPENTARGET平台构建PDHA1的基因-疾病网络,登录cBioportal网站分析PDHA1的遗传变异,使用TIMER和GEPIA数据库,分析PDHA1表达与BRCA中免疫浸润细胞及其标志物的关系,并对PDHA1共表达基因进行GO,KEGG富集分析;通过miRcode、miRTarBase、TargetScan、miRDB数据库分析,构建乳腺癌ceRNA调控网络。结果:PDHA1基因在乳腺癌组织中低表达,其表达水平在乳腺癌患者T期、人种、组织分型,分子分型中具有统计学差异;免疫组化实验提示PDHA1蛋白在BRCA染色呈低水平;遗传变异分析提示基因扩增和突变是PDHA1在乳腺癌中最常见的遗传改变。免疫浸润分析显示PDHA1的表达与BRCA中免疫细胞浸润水平相关。PDHA1共表达基因功能富集于染色体分离,DNA复制,细胞周期通路等。最后得到与PDHA1相关的7个miRNA,38个lncRNA参与构建乳腺癌ceRNA调控网络。结论:PDHA1在乳腺癌中呈低表达,PDHA1表达水平与BRCA中ceRNA网络和免疫浸润相关,为进一步研究乳腺癌的遗传变异、发生发展提供了初步基础。Objective To comprehensively analyze the expression and the biological role of the pyruvate dehydrogenase E1αsubunit(PDHA1)in breast cancer using bioinformatics methods and clinical sample experiments.Methods TCGA and GTEx databases were mined to explore the mRNA expression levels of PDHA1 in breast cancer and normal tissues;clinical samples were collected from our hospital for immunohistochemistry experiments to verify the expression of PDHA1 proteins;The gene-disease network of PDHA1 was constructed on the OPENTARGET platform,and the cBioportal website was accessed to analyze the genetic variations of PDHA1,using the TIMER and GEPIA databases to analyze the relationship between PDHA1 expression and immune infiltrating cells and their markers in BRCA,analyzing the GO and KEGG enrichment of PDHA1 co-expressed genes.The breast cancer ceRNA regulatory network was constructed by miRcode,miRTar-Base,TargetScan,and miRDB database analysis.Results The PDHA1 gene was lowly expressed in breast cancer tissues,which was statistically different in patients'clinical stage,T stage,ethnicity,tissue typing,and molecular typing;immunohistochemistry experiments of clinical samples suggested that the PDHA1 protein was lowly stained with BRCA staining;genetic variant analysis suggested that gene amplification and mutation were the most common genetic alterations of PDHA1 in breast cancer.Analysis of the TIMER and GEPIA databases showed that PDHA1 expression was associated with immune cell infiltration.The functions of PDHA1 co-expressed genes were enriched in chromosome segregation,DNA replication,and cell cycle pathways.Correlation analysis showed that 7 miRNAs and 38 lncRNAs associated with PDHA1 were involved in the construction of the breast cancer ceRNA regulatory network.Conclusion PDHA1 was lowly expressed in the breast cancer and associated with the ceRNA network and immune infiltration.The DEG and pathways identified in this study provide a preliminary basis for further research on the occurrence and development of the br

关 键 词：乳腺癌 丙酮酸脱氢酶E1亚基α1(PDHA1) 遗传变异 免疫浸润 ceRNA 

分 类 号：R737.9[医药卫生—肿瘤]