张桐硕,刘金龙,赵跃,王朵朵,宋姜楠,陈晓,郭小芹,李艳秋,祝峰.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[J].转化医学杂志,2020,9(4):197-201
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 cancer and the mechanism based on bioinformatics
  
DOI:
中文关键词:  上皮性卵巢癌  白细胞介素-6  生物信息学分析  病程监测
英文关键词:Epithelial ovarian cancer (EOC)  Interleukin-6(IL-6)  Bioinformatics analysis  Procession monitoring
基金项目:国家自然科学基金(81502256)
作者单位
张桐硕 武警江苏省总队医院检验与病理科武警特色医学中心 
刘金龙 解放军31696部队卫生连武警特色医学中心 
赵跃 武警第一机动总队医院外科武警特色医学中心 
王朵朵 安徽医科大学研究生院 
宋姜楠 武警特色医学中心 
陈晓 武警特色医学中心 
郭小芹 武警后勤学院病原生物学教研室 
李艳秋 武警特色医学中心 
祝峰 武警江苏省总队医院检验与病理科 
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中文摘要:
      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 cancer,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 omnibus,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FIGO Ⅰ~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FIGO Ⅰ~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。
英文摘要:
      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. MethodsQuantification 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 significant 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. ResultsThe 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 stage Ⅰ~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 FIGO Ⅰ~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. ConclusionSerum 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-5.
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