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中国癌症防治杂志

中国癌症防治杂志 ›› 2014, Vol. 6 ›› Issue (3): 235-243.doi: 10.3969/j.issn.1674-5671.2014.03.04

• 基础研究 • 上一篇    下一篇

广西扶绥地区黄曲霉毒素B1相关性肝细胞癌蛋白质表达谱分析

  

  1. 广西医科大学附属肿瘤医院肝胆外科；广西扶绥县人民医院普通外科；广西肿瘤防治研究所实验研究部
  • 出版日期:2014-09-25 发布日期:2014-10-17
  • 通讯作者: 齐鲁楠 E-mail:wangzhennuo@aliyun.com
  • 基金资助:

    广西自然科学基金资助项目（2013GXNSFBA019196）

Proteomic analysis of aflatoxin B1-related hepatocellular carcinoma in the FuSui area of  Guangxi，China

  • Online:2014-09-25 Published:2014-10-17

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摘要： 目的 研究广西扶绥地区黄曲霉毒素B1（aflatoxin B1，AFB1）相关性肝细胞癌（hepatocellular carcinoma，HCC）的差异蛋白质表达谱，筛选与AFB1暴露相关的肝癌分子标志物，并初步探讨AFB1的致肝癌机制。方法 40例HCC组织按照AFB1的暴露情况分为两个亚组：A组为AFB1暴露组（24例），B组为非AFB1暴露组（16例），同时收集10例来自肝血管瘤、肝外伤、肝移植供体等手术切除的正常肝组织作为正常对照。应用iTRAQ结合2DLC-MS/MS技术分析蛋白质表达谱在各组间的差异。结果 按照组间差异参数ratio>2.0（上调）或ratio<0.5（下调）为筛选标准，两个亚组共鉴定出差异蛋白88种（上调的蛋白51种，下调的蛋白37种），其中50种差异蛋白在两个亚组中均有相同变化趋势，其余38种差异蛋白则存在AFB1暴露的病因学特异性。通过GO注释对筛选出的差异蛋白进行分类分析，88种差异蛋白主要定位于细胞质、细胞核及线粒体，以结合功能和催化功能相关蛋白为主，主要参与毒物代谢调节、应激反应及抗凋亡等生物学过程。结论 本研究筛选出多种与AFB1暴露相关性HCC的差异蛋白，为探讨广西扶绥AFB1高暴露地区的HCC发病机制提供了新的线索。

关键词: 肝肿瘤, 黄曲霉毒素B1, 蛋白质组学, iTRAQ技术

Abstract: Objective To establish specific molecular marker profiles of aflatoxin B1（AFB1）-related hepatocellular carcinoma （HCC）by comparing protein expression profiles between AFB1-related and non-AFB1-related HCC in the FuSui area of Guangxi. Method A total of 24 patients with AFB1-related HCC and 16 patients with non-AFB1-related HCC group were analyzed by isobaric tagging reagent （iTRAQ） quantitative proteomics together with 2DLC-MS/MS in order to identify differences in protein expression levels.In parallel，normal liver tissue from 10 patients who were liver donors，who had hepatic hemangioma or who had undergone liver resection was analyzed as a control. Results A total of 88 unique proteins were identified that were ≥2-fold overexpressed（51 proteins） or≤0.5-fold underexpressed（37 proteins） in AFB1-related HCC tissue relative to control tissue.Of the 88 proteins，50 were expressed at similar levels in AFB1-related HCC and non-AFB1-related HCC tissue，while 38 were associated with pathological features.Based on gene ontology analysis， most of the 88 proteins are predicted to play roles as binding proteins and catalysts.Most are located in the cytoplasm，nucleus or mitochondria，and most are involved in detoxification，drug metabolism and anti-apoptotic pathways. Conclusions This study has identified several differentially expressed proteins associated with AFB1-related HCC in the FuSui area of Guangxi，which may provide clues to understanding AFB1-related hepatocarcinogenesis in this part of the world.

Key words: Liver neoplasm, Aflatoxin B1, Roteomics, iTRAQ