肺腺癌关键基因的筛选及分泌型磷酸蛋白1在肺腺癌中的表达  

Screening of key genes of lung adenocarcinoma and expression of secreted phosphoprotein 1 in lung adenocarcinoma

作　　者：赵丹 王俊苹 牟海军 王显艳 毕红霞 郑红艳 孔维丽 李晶 程薪樾 ZHAO Dan;WANG Junping;MU Haijun;WANG Xianyan;BI Hongxia;ZHENG Hongyan;KONG Weili;LI Jing;CHENG Xinyue(Department of Pathogen Biology,Medical Technology School,Qiqihar Medical University,Qiqihar,Heilongjiang,161006,China;Department of Respiratory and Critical Care Medicine,the Third Affiliated Hospital of Qiqihar Medical University,Qiqihar,Heilongjiang,161005,China)

机构地区：[1]齐齐哈尔医学院医学技术学院病原生物学教研室,黑龙江齐齐哈尔161005 [2]齐齐哈尔医学院附属第三医院呼吸与危重症医学科,黑龙江齐齐哈尔161006

出　　处：《当代医学》2023年第34期21-29,共9页Contemporary Medicine

基　　金：黑龙江省教育厅基金项目(2019-KYYWF-1216)。

摘　　要：目的基于美国国家生物技术信息中心(NCBI)基因表达数据库(GEO)和美国国家癌症研究所(NCI)癌症基因组图谱(TCGA)联合生物学信息分析筛选肺腺癌关键基因(HUB)及相关信号通路、分泌型磷酸蛋白1(SPP1)表达及与肺腺癌患者临床特征的相关性。方法从GEO数据库下载包括肺腺癌与正常或癌旁肺组织基因表达2个数据集GSE10072、GSE43458,收集2020年1月至2021年3月于齐齐哈尔医学院附属第三医院行手术治疗且病理明确诊断为肺腺癌患者的癌组织和癌旁标本作为肺腺癌临床验证数据集(QY3F)并进行标准化及处理,筛选出肺腺癌与正常肺组织之间的差异基因,并进行基因本体(GO)功能、京都基因与基因组百科全书(KEGG)通路富集分析;通过筛选出的差异基因构建蛋白质相互作用网络(PPI),分析并筛选HUB基因;通过TCGA数据集验证SPP1表达及与肺腺癌患者临床特征和预后的相关性;通过QY3F验证SPP1表达及与肺腺癌患者临床特征的相关性;通过TCGA数据库分析肺腺癌患者SPP1基因与相关通路的相关性。结果通过2个GEO数据集筛选出差异表达基因120个,上调表达23个,下调表达97个。GO功能富集分析结果显示,差异基因参与细胞外基质组织及细胞膜结构的形成和功能及调节细胞对生长因子刺激的反应、骨小梁形成、肽及糖胺聚糖绑定;KEGG通路富集分析结果显示,差异基因参与细胞外基质的黏附、蛋白质消化吸收及过氧化物酶体增殖物激活受体(PPAR)信号通路。筛选出前10的HUB基因分别为DNA拓扑异构酶Ⅱα(TOP2A)、基质金属蛋白酶9(MMP9)、SPP1、基质金属蛋白酶抑制剂1(TIMP1)、羟基类固醇17-β脱氢酶6(HSD17B6)、细胞周期蛋白B1(CCNB1)、尿激酶型纤维蛋白溶酶原激活因子(PLAU)、丝氨酸/苏氨酸蛋白激酶(PBK)、周期蛋白依赖激酶抑制因子3(CDKN3)和人Ⅰ型胶原α1(COL1A1)。10个HUB基因中,除HSD17B6在TCGA数据库肺腺癌患者癌�Objective Based on the National Center for Biotechnology Information(NCBI)gene expression omnibus(GEO)and National Can-cer Institute(NCI)the cancer genome atlas(TCGA)databases combined with biological information to analyze and screen key genes(HUB)and asso-ciated signaling pathways secreted phosphoprotein1(SPP1)expression and their correlation with clinical characteristics of lung adenocarcinoma pa-tients.Methods 2 data sets GSE10072 and GSE43458 were downloaded from GEO database,including gene expression of lung adenocarcinoma and normal or adjacent lung tissue,the cancer tissues and adjacent samples of patients with lung adenocarcinoma who underwent surgical treatment and were pathologically diagnosed in the Third Affiliated Hospital of Qiqihar Medical University from January 2020 to March 2021 were collected as the clinical validation data set of lung adenocarcinoma(QY3F)and standardized and processed,the differential genes between lung adenocarcinoma and normal lung tissue were screened,and gene ontology(GO)function and kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed;protein-protein interaction networks(PPI)was constructed by the screened differential genes,and HUB genes were ana-lyzed and screened;the TCGA data set was used to verify the expression of SPP1 and its correlation with clinical characteristics and prognosis of lung adenocarcinoma patients;the QY3F data set was used to verify the expression of SPP1 and its correlation with the clinical characteristics of lung adenocarcinoma patients;TCGA database was used to analyze the correlation between SPP1 gene and related pathways in lung adenocarcinoma pa-tients.Results 120 differentially expressed genes were screened out from the 2 GEO datasets,including 23 up-regulated genes and 97 down-regulat-ed genes.GO functional enrichment analysis showed that differential genes were involved in the formation and function of extracellular matrix tissue and cell membrane structure,and regulated cell response to growth factor st

关 键 词：肺腺癌 分泌型磷酸蛋白1 生物标志物 生物信息学 关键基因 

分 类 号：R734.2[医药卫生—肿瘤]