宫颈癌癌组织中差异表达蛋白的蛋白组学研究  

Proteomics study of differentially expressed proteins in cervical cancer

作　　者：海静[1] 李文娟[2] 王文翔[1] 杨静[1] 董学彩[1] HAI Jing;LI Wen-juan;WANG Wen-xiang;YANG Jing;DONG Xue-cai(Department of Obstetrics and Gynecology,Xinxiang Central Hospital,Xinxiang 453000,Henan,China;不详)

机构地区：[1]新乡市中心医院妇产科,河南新乡453000 [2]辽宁省人民医院妇产科,辽宁沈阳110016

出　　处：《广东医学》2023年第2期138-144,共7页Guangdong Medical Journal

基　　金：辽宁省自然科学基金项目(201805500314);河南省医学科技攻关计划联合共建项目(LHGJ20210899)。

摘　　要：目的通过蛋白组学技术探讨宫颈癌癌组织中的差异表达蛋白。方法纳入于新乡市中心医院就诊的12例宫颈癌患者和12例宫颈活检结果正常者作为研究对象。将24例研究对象分为实验组和验证组,其中10例宫颈癌患者和10例宫颈活检正常者构成实验组,其余2例宫颈癌患者和2例宫颈活检正常者构成验证组。通过蛋白组学技术探讨宫颈癌患者(n=10例)癌组织与正常宫颈组织(n=10例)中的差异表达蛋白,并将差异表达蛋白进行GO富集和KEGG富集分析,通过蛋白互作(protein protein interaction,PPI)分析筛选出与宫颈癌发病机制相关的关键蛋白,选取5种相关度最为显著的蛋白在验证组中进行Western blot验证。结果共有4718个蛋白被定量分析,相对于正常宫颈组织,宫颈癌癌组织中显著上调的蛋白有190个,显著下调的蛋白有163个。对发生显著改变的353个蛋白进行GO富集分析和KEGG富集分析,结果显示,差异蛋白涉及的生物学过程主要为中性粒细胞活化、氧化应激、免疫应答及急性相反应等,差异蛋白主要涉及IL-17信号通路、人乳头瘤病毒感染相关通路、PI3K-AKT信号通路、氧化磷酸化、MAPK信号通路等。PPI分析筛选出109个差异蛋白,主要涉及到免疫炎症、氧化应激、IL-17信号通路等。IKKβ、CDK2、COX4、AKT和Ras蛋白是PPI结果中相关度最为显著的前5种蛋白,Western blot结果显示,宫颈癌癌组织中IKKβ、CDK2、COX4、p-AKT和Ras蛋白表达水平显著升高,差异均具有统计学意义(P<0.05)。结论蛋白组学技术筛选出可能参与宫颈癌发生发展的相关蛋白及免疫学信号通路,为宫颈癌的发病机制和治疗靶点进一步提供了方向。Objective To investigate the differentially expressed proteins in cervical cancer tissues via proteomics technology.Methods A total of 12 patients with cervical cancer and 12 patients with normal histopathology results of cervical biopsy in Xinxiang Central Hospital were enrolled.The 24 individuals were divided into experimental group and verification group.The 10 patients with cervical cancer and 10 patients with normal histopathology results of cervical biopsy were included into experimental group,and the remaining individuals into verification group.The differentially expressed proteins between cervical cancer tissues and normal histopathology results of cervical biopsy was explored by proteomics technology.The differentially expressed proteins were further analyzed by GO and KEGG enrichment analysis.The protein protein interaction(PPI)analysis was used to screen out the key proteins in the etiology of cervical cancer.Five proteins with the most significant correlation with each other and were selected for Western blot verification in verification group.Results A total of 4718 proteins were quantitatively analyzed.Compared with normal cervical tissues,there were 353 proteins significantly changed in cervical cancer tissues,of which 190 were up-regulated and 163 were down-regulated.The 353 proteins were further analyzed by GO and KEGG enrichment analysis.And the results showed that the enriched biological processes mainly involved with neutrophil activation,oxidative stress,immune response,and acute phase response.The protein involved mainly with IL-17 signaling pathway,human papillomavirus infection-related pathway,PI3K-AKT signaling pathway,oxidative phosphorylation,and MAPK signaling pathway.A total of 109 differential proteins were screened after PPI analysis and these proteins were mainly related to immune inflammation,oxidative stress,and IL-17 signaling pathway.The top five proteins were IKKβ,CDK2,COX4,AKT and Ras.Western blot results show that the expression levels of IKKβ,CDK2,COX4,p-AKT and Ras prot

关 键 词：宫颈癌 蛋白组学 炎症 细胞增殖 

分 类 号：R711[医药卫生—妇产科学] R737.33[医药卫生—临床医学]