CAJ | 학술논문

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。
목적：연구엄서부수지구황곡매독소B1（aflatoxin B1，AFB1）상관성간세포암（hepatocellular carcinoma，HCC）적차이단백질표체보，사선여AFB1폭로상관적간암분자표지물，병초보탐토AFB1적치간암궤제。방법40례HCC조직안조AFB1적폭로정황분위량개아조：A조위AFB1폭로조（24례），B조위비AFB1폭로조（16례），동시수집10례래자간혈관류、간외상、간이식공체등수술절제적정상간조직작위정상대조。응용iTRAQ결합2DLC-MS/MS기술분석단백질표체보재각조간적차이。결과안조조간차이삼수ratio>2.0（상조）혹ratio<0.5（하조）위사선표준，량개아조공감정출차이단백88충（상조적단백51충，하조적단백37충），기중50충차이단백재량개아조중균유상동변화추세，기여38충차이단백칙존재AFB1폭로적병인학특이성。통과GO주석대사선출적차이단백진행분류분석，88충차이단백주요정위우세포질、세포핵급선립체，이결합공능화최화공능상관단백위주，주요삼여독물대사조절、응격반응급항조망등생물학과정。결론본연구사선출다충여AFB1폭로상관성HCC적차이단백，위탐토엄서부수AFB1고폭로지구적HCC발병궤제제공료신적선색。
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.