应用iTRAQ技术筛选不同生存期食管癌患者的血清差异蛋白  

Screening of serum differential proteins in esophageal cancer patients with different survival time by using iTRAQ technology

作　　者：马晓丽[1] 刘娟[1] 曹雷雨[1] 张建清[1] 张倩[1] 张莉[1] Ma Xiaoli;Liu Juan;Cao Leiyu;Zhang Jianqing;Zhang Qian;Zhang Li(VIP Department of Internal Medicine,The First Affiliated Hospital of Xinjiang Medical University,Xinjiang Urumqi 830054,China)

机构地区：[1]新疆医科大学第一附属医院内科VIP

出　　处：《现代肿瘤医学》2019年第20期3611-3616,共6页Journal of Modern Oncology

基　　金：国家自然科学基金资助项目(编号:81460754)

摘　　要：目的:应用同位素标记相对和绝对定量(iTRAQ)技术筛选血清差异蛋白,为临床个性化治疗和判断疾病的预后提供参考依据。方法:选取确诊为局部晚期和晚期食管鳞癌患者52例,进行常规放疗和化疗,观察疗效并随访,随访时间截止至2018年04月。根据不同生存期进行分组,应用iTRAQ技术筛选与食管癌患者生存期长短有关系的血清差异蛋白。观察这些差异蛋白的生物学特点,利用KEGG数据库将与肿瘤生存相关的优势蛋白筛选出来。结果:将不同生存期食管癌患者之间的血清差异蛋白筛选出来之后,发现有42个差异性表达明显的蛋白,分为表达上调的蛋白和表达下调的蛋白,分别是19个和23个。此外还有4个血清差异蛋白同时出现在两组间,包括1个同时上调蛋白和3个同时下调蛋白,分别是血清淀粉样A-2蛋白质(SAA2)和血浆丝氨酸蛋白酶抑制剂(SERPINA5)、组蛋白H4(HIST1H4A)以及组蛋白H3.1(HIST1H3A)。SERPINA5与生存期较长相关;HIST1H4A、HIST1H3A出现在生存期较短的一组中。KEGG数据库的分析发现,在Viral carcinogenesis、Transcriptional misregulation in cancer信号通路的调节中可能有H4、H3.1的参与。结论:在局部晚期或晚期食管鳞癌患者外周血中筛选出的一些潜在优势蛋白,经过研究发现其与食管鳞癌患者生存期长短有关,并参与一些关键通路。对食管鳞癌预后风险判断具有潜在预测价值的有HIST1H4A、HIST1H3A和SERPINA5。Objective: To screen serum differentially expressed proteins by using isotope labeled relative and absolute quantitative( i TRAQ),which is closely related to the survival time of esophageal cancer,and to provide a reference for individualized treatment and prognosis of esophageal cancer. Methods: A total of 52 patients with locally advanced and advanced esophageal squamous cell carcinoma were enrolled in this study. The patients were treated with conventional radiotherapy and chemotherapy then the therapeutic effect was observed and evaluated and long-term follow-up was maintained. The survival time after radiotherapy and chemotherapy was determined,and the follow-up time ended to April 2018. Grouping according to different lifetimes and applying i TRAQ technology to filter serum differentially expressed proteins associated with survival time of esophageal carcinoma. Then the biological characteristics of these differently expressed proteins were analyzed and the dominant proteins related to tumor survival were screened out by using KEGG database. Results: After screening the serum differential proteins between different survival periods of esophageal cancer patients,42 differentially expressed proteins were found,which were up-regulated proteins and down-regulated proteins. The numbers were 19 and 23,respectively. In addition,there were 4 serum differential proteins in both groups,which included one up-regulated protein and three down-regulated proteins. SAA2 serum amyloid A-2 protein and SERPINA5 plasma serine protease inhibitor,HIST1 H4 A histone H4 and HIST1 H3 A histone H3. 1. SERPINA5 was associated with a longer survival period,while HIST1 H4 A,HIST1 H3 A appeared in a shorter group. According to the analysis of KEGG database,the regulation of viral carcinogenesis,transcriptional misregulation in cancer signaling pathway may involve H4,H3. 1. Conclusion:Some potential predominance proteins in peripheral blood of patients with locally advanced or advanced esophageal squamous cell carcinoma were found to be

关 键 词：食管鳞癌 蛋白质组学 放化疗 生存 预后 

分 类 号：R735.1[医药卫生—肿瘤]