整合素连接激酶在食管鳞状细胞癌中的表达和生物信息分析  

Expression and bioinformatics analysis of integrin linked kinase in esophgeal squamous cell carcinoma

作　　者：刘娟[1] 魏瑜[1] 高艳 曹雷雨[1] 马晓丽[1] 张莉[1] LIU Juan;WEI Yu;GAO Yan;CAO Leiyu;MA Xiaoli;ZHANG Li(Fourth Department of General Internal Medicine/Special Needs Medicine,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China)

机构地区：[1]新疆医科大学第一附属医院综合内四科/特需内科,乌鲁木齐830054

出　　处：《新疆医科大学学报》2022年第6期581-587,共7页Journal of Xinjiang Medical University

基　　金：国家自然科学基金地区基金(81860421)。

摘　　要：目的基于生信数据挖掘整合素连接激酶(Integrin linked kinase,ILK)参与食管鳞癌的潜在机制,探讨ILK在食管鳞状细胞癌(简称食管鳞癌)中的表达及临床意义。方法收集2008年7月-2015年4月在新疆医科大学第一附属医院肿瘤科诊断为食管鳞癌的52例患者血液标本作为实验组。同期年龄、性别相匹配的健康体检者26例作为正常对照组。利用同位素相对和绝对定量(iTRAQ)技术筛选出参与食管鳞癌的差异蛋白,通过实时荧光定量PCR(qRT-PCR)、蛋白免疫印迹(Western blot,WB)法验证其在食管鳞癌与正常食管上皮细胞中的表达;运用UALCAN分析食管鳞癌芯片中ILK表达与预后相关性;利用Linked Omics和Cytoscape软件获得ILK共表达基因集,并进行基因功能分类体系(Gene ontology,GO)和京都基因和基因组百科全书(Kyoto encyclopedia of genes and ge-nomes,KEGG)富集分析;结合String和Cytoscape筛选出前10位的核心基因(Hub gene)并构建蛋白质-蛋白质相互作用网络图(PPI);通过GEPIA分析Hub gene mRNA水平在食管癌组织中的表达及预后关系。结果ILK在食管鳞癌患者血清中高表达(P<0.05);qRT-PCR、Western blot法结果显示,食管鳞癌TE-1和KYSE150细胞中的ILK相对表达量均显著高于正常食管上皮SHEE细胞(P<0.05);相同病理组织分化程度下,ILK高表达可显著降低食管鳞癌患者总生存期(P<0.05);Linked Omics分析获得175个共表达基因;GO分析生物学过程主要富集在金属内肽酶抑制剂活化、负调控通路受限的SMAD蛋白磷酸化等,细胞组成主要在细胞外基质、细胞骨架等,分子功能主要为整合素结合、生长因子结合等;KEGG富集在细胞外基质受体相互作用、TGFβ信号通路、黏附等。PPI分析筛选出前10位的核心基因,如FN1等,数据库分析显示有9个在食管癌中异常表达,FN1和BGN高表达与患者无病生存期减少显著相关。结论ILK参与食管鳞癌的发生、发展,ILK的高表达对食管鳞Objective To analyze the expression and clinical significance of Integrin Linked Kinase(ILK)in esophageal squamous cell carcinoma,to explore the potential mechanism of ILK involvement in esophageal squamous cell carcino⁃ma with bioinformatics methods.Methods Blood samples from 52 patients diagnosed with esophageal squamous carci⁃noma in the hospital from July 2008 to April 2015 were collected as the experimental group.26 age-matched and sex matched health examination subjects were used as the normal control group.The research screened out the markedly differentiated proteins by isotope relative and absolute quantification(iTRAQ)within the two groups,and its expres⁃sions in esophageal squamous cell carcinoma and normal esophageal epithelial cells were detected by real-time fluo⁃rescent quantitative PCR(qRT-PCR)and Western blot(WB).UALCAN was used to analyze the correlation between ILK expression and prognosis in esophageal cancer microarray.ILK co-expression genes were obtained by Using LinkedOmics and Cytoscape software,and GO and KEGG enrichment analysis was performed.Combining String and Cytoscape,the top 10 Hub-genes were screened out;PPI was constructed.GEPIA was used to analyze the expression and prognosis of Hub-gene mRNA levels in esophageal cancer tissues.Results ILK was highly expressed in serum of the patients with esophageal squamous cell carcinoma(P<0.05).qRT-PCR and WB confirmed that the relative expres⁃sion levels of ILK inTE-1 and KYSE150 were significantly higher than in SHEE(P<0.05).In same degree of pathologi⁃cal differentiation,ILK expression with high level could significantly reduce the overall survival in ESCC patients(P<0.05).LinksedOmics analysis revealed 175 ILK co-expressed genes.The biological processes of GO analysis were mainly concentrated in activation of peptidase inhibitors within metals and phosphorylation of SMAD proteins with lim⁃ited negative regulatory pathways.Cell composition was mainly in extracellular matrix and cytoskeleton,and molecular functions were main

关 键 词：整合素连接激酶 食管鳞癌 数据库 分子机制 

分 类 号：R735.1[医药卫生—肿瘤]