摘要
目的鉴定肝细胞癌(hepatocellular carcinoma,HCC)特异性血清细胞因子。方法用细胞因子抗体芯片检测非癌对照和HCC患者血清细胞因子,富集分析KEGG生物学通路,ProteoMap分析生物学功能构成。构建基于STRING数据库差异表达细胞因子间相互作用网络,计算节点分子的“degree”和“betweenness”,确定关键细胞因子并应用ELISA进行验证。结果鉴定出差异倍数>1.5倍的HCC相关差异表达细胞因子为43个(高、低表达分别为26个和17个),80%差异表达的细胞因子参与多个功能相关的生物学通路和信号通路。这些差异表达细胞因子构成的蛋白-蛋白互作网络中,“degree”和“betweenness”分值位居前5的细胞因子包括VEGFA、VCAM1、CXCR4、CCR7和TLR3。HCC血清中VEGFA、CCR7和CXCR4表达显著高于肝硬化和慢性乙肝患者及健康对照,其中慢性乙肝患者血清VEGFA表达高于肝硬化和健康对照,慢性乙肝和肝硬化患者血清中CCR7和CXCR4表达差异无统计学意义,但明显高于健康对照。结论VEGFA、CCR7和CXCR4是潜在的HCC血清标志物。
Objective To identify the hepatocellular carcinoma(HCC)-specific cytokines with differential expression.Methods Serum cytokines in non-cancer control and HCC patients were profiled by cytokine antibody microarray.Enrichment of KEGG biological pathways was analyzed by DAVID and the makeup of biological functions was analyzed by ProteoMap.After construction of a protein-protein interaction network based on differentially expressed cytokines,the“degree”and“betweenness”of the node molecules were calculated to identify the key cytokines associated with HCC,which were validated by ELISA.Results Forty-three differentially expressed cytokines associated with HCC,including 26 up-regulated and 17 down-regulated,respectively,were identified,and 80%of these differentially expressed cytokines were involved in multiple functionally related biological pathways and signaling pathways.A protein-protein interaction network based on these differentially expressed cytokines were constructed using STRING database,and the top 5 cytokines with high“degree”and“betweenness”scores included VEGFA,VCAM1,CXCR4,CCR7 and TLR3.The levels of VEGFA,CCR7 and CXCR4 in serum of HCC patients were significantly higher than those in cases with liver cirrhosis,chronic hepatitis B infection and healthy controls.The serum levels of VEGFA in cases with chronic hepatitis B were higher than those with cirrhosis and healthy controls.The levels of CCR7 and CXCR4 in serum of patients with chronic hepatitis B and cirrhosis were not significantly different,but significantly higher than those in healthy controls.Conclusion VEGFA,CCR7 and CXCR4 are potential serum biomarkers of HCC.
作者
张迷
陈曦
李孟祥
焦叶林
齐义军
岳文彬
ZHANG Mi;CHEN Xi;LI Mengxiang;JIAO Yelin;QI Yijun;YUE Wenbin(Department of Oncology,Puyang Oilfield General Hospital Affiliated to Xinxiang Medical University,Puyang 457001;School of Information Engineering,He’nan University of Science and Technology;Department of Pathology,Luoyang First People’s Hospital;He’nan Key Laboratory of Cancer Epigenetics Medical College,He’nan University of Science and Technology,China)
出处
《胃肠病学和肝病学杂志》
CAS
2021年第11期1224-1229,共6页
Chinese Journal of Gastroenterology and Hepatology
基金
河南省科技攻关项目(152102310218)。
