IL-6与上皮性卵巢癌分期进展关系及其作用机制的生物信息学分析  

Analysis of the relationship between IL-6 and staging progression of epithelial ovarian cancerand the mechanism based on bioinformatics

作　　者：张桐硕 刘金龙 赵跃 王朵朵 宋姜楠 陈晓 郭小芹[6] 李艳秋 祝峰[1] ZHANG Tongshuo;LIU Jinlong;ZHAO Yue;WANG Duoduo;SONG Jiangnan;CHEN Xiao;GUO Xiaoqin;LI Yanqiu;ZHU Feng(Department of Laboratory and Pathology,Jiangsu Provincial Corps Hospital of PAP,Yangzhou Jiangsu 225003,China;Hygiene Company,Unit 31696 of PLA,Jinzhou Liaoning 121000,China;Departmentof Surgery,First Mobile Corps Hospital of PAP,Dingzhou Hebei 073000,China;Graduate School,AnhuiMedical University,Hefei Anhui 230032,China;Special Medical Center of PAP,Tianjin 300162,China;Department of Pathogenic Biology,Logistics University of PAP,Tianjin 300309,China)

机构地区：[1]武警江苏省总队医院检验与病理科,江苏扬州225003 [2]解放军31696部队卫生连,辽宁锦州121000 [3]武警第一机动总队医院外科,河北定州073000 [4]安徽医科大学研究生院,安徽合肥230032 [5]武警特色医学中心,天津300162 [6]武警后勤学院病原生物学教研室,天津300309

出　　处：《转化医学杂志》2020年第4期197-201,共5页Translational Medicine Journal

基　　金：国家自然科学基金(81502256)。

摘　　要：目的探讨白细胞介素-6(interleukin-6,IL-6)表达水平在上皮性卵巢癌(epithelial ovarian canc-er,EOC)中的临床价值,并基于生物信息学预测IL-6对EOC发生、发展的潜在机制.方法ELISA法检测21例不同国际妇产科联盟(International Federation of Gynecology and Obstetrics,FIGO)手术-病理分期的EOC患者、12例良性卵巢疾病患者和30例健康体检妇女的血清IL-6水平.从公共基因表达(gene expression omni-bus,GEO)数据库和癌症基因组图谱(the cancer genome atlas,TCGA)数据库收集共计897例EOC组织样本的基因表达谱,根据IL-6高低表达分组筛选差异基因,进行GO和KEGG通路富集分析.绘制IL-6相关基因所编码蛋白的相互作用网络图,提取IL-6所在的核心网络模块.结果血清IL-6在EOC患者的水平显著高于正常对照组(P=0.031),与FIGOⅠ~Ⅳ期呈正相关(r=0.79,P=0.002);基于TCGA数据库挖掘的IL-6基因表达水平在发生脉管浸润时上调(P=0.027),且随FIGOⅠ~Ⅲ依次升高;从4个卵巢癌数据集筛选出199个共同差异基因,富集于细胞外基质重塑、细胞粘附、炎性反应、病原体免疫识别等功能和相应的信号通路;初步鉴定出CCL2、PTPRC、CD163可能为IL-6在EOC中发挥作用的关键分子.结论血清IL-6可为EOC的复发和转移提供实验室证据,生物信息学分析提示IL-6相关基因主要与EOC的侵袭和转移等生物学特性有关,IL-6用于评估病情进展的具有临床意义.Objective To explore the clinical value of serum interleukin-6(IL-6)in epithelial ovarian cancer(EOC),and predict the potential mechanism of IL-6 for the occurrence and development of EOC based on bioinformatics analysis.Methods Quantification of IL-6 serum protein level was performed using ELISA in 21 patients with EOC at various International Federation of Gynecology and Obstetrics(FIGO)stages(EOC group),12 patients with benign ovarian disease(benign disease group)and 30 healthy women passing the medical examination(control group).There were a total of 897 gene expression profiles of EOC tissue samples were downloaded from gene expression omnibus(GEO)and the cancer genome atlas(TCGA)databases.The genes with signifi cant difference were screened from two groups respectively with high and low expression level of IL-6.The GO and KEGG pathway analysis were performed.Besides,protein-protein interaction network was established and module analysis of that network was performed using MCODE.Results The IL-6 serum level in EOC group was significantly higher than that in the control group(P=0.031).Spearman correlation analysis showed IL-6 serum level was positively correlated with FIGO stageⅠ~Ⅳ(r=0.79,P=0.002).The IL-6 gene expression level based on TCGA database was up-regulated in the samples with vascular invasion(P=0.027),and increased with FIGOⅠ~Ⅲ.Based on 4 human EOC datasets,199 common differenced genes were identified,which were enriched in extracellular matrix remodeling,cell adhesion,inflammatory response,immune recognition against pathogen and related signaling pathways.Furthermore,CCL2,PTPRC and CD163 were preliminarily deemed the key molecules being related to the effect of IL-6 in EOC.Conclusion Serum IL-6 can provide laboratory evidence for recurrence and metastasis of EOC.Bioinformatics analysis indicates that IL-6 related genes are mainly for invasion and metastasis of EOC,which verifies the clinical value of IL-6.

关 键 词：上皮性卵巢癌 白细胞介素-6 生物信息学分析 病程监测 

分 类 号：R737.31[医药卫生—肿瘤] Q-3[医药卫生—临床医学]