上海交通大学学报（医学版）

›› 2012, Vol. 32 ›› Issue (9): 1185-.doi: 10.3969/j.issn.1674-8115.2012.09.013

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分子标志物在胃癌发病机制及转化医学研究中的应用

朱正纲1, 傅国辉2, 刘炳亚1, 于颖彦1, 瞿 颖1, 吴云林1, 顾琴龙1, 李建芳1, 李 琛1, 严 超1, 张 俊1, 刘文韬1, 燕 敏1, 沈炜炜2, 程时丹1   

  1. 上海交通大学 1.医学院附属瑞金医院外科 上海消化外科研究所 上海市胃肿瘤重点实验室, 上海 200025； 2.基础医学院病理学教研室, 上海 200025
  • 出版日期:2012-09-28 发布日期:2012-09-29
  • 作者简介:朱正纲（1954—）, 男, 教授, 博士, 博士生导师, 现任上海交通大学医学院附属瑞金医院院长、上海交通大学瑞金临床医学院院长；电子信箱: zzg1954@hotmail.com。
  • 基金资助:

    国家科技支撑计划(“十一五”）（2008BA152B03）；国家科技支撑计划(“十二五”）（2011BA203191）；国家自然科学基金（30872476, 30872477, 30801371, 30901729, 30972871, 30973486, 30900670, 81072012, 81101847, 81172324, 81101585, 81172329）；上海市科委（生药重大）项目（09DZ1950100）；上海市科委（基础重点）基金（09JC1409600, 10JC1411100）；上海市教委重点基金（12zz105, 12zz102）

Mechanisms and translational research based on molecular biomarkers of gastric cancer

ZHU Zheng-gang1, FU Guo-hui2, LIU Bing-ya1, YU Ying-yan1, QU Ying1, WU Yun-lin1, GU Qin-long1, LI Jian-fang1, LI Chen1, YAN Chao1, ZHANG Jun1, LIU Wen-tao1, YAN Min1, SHEN Wei-wei2, CHENG Shi-dan1   

  1. 1.Department of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China；2.Department of Pathology, Basic Medical College, Shanghai Jiaotong University, Shanghai 200025, China
  • Online:2012-09-28 Published:2012-09-29

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摘要：

该项目以分子标志物为切入点，以高通量组学技术为基础，筛选出胃癌相关的分子标志物，对胃癌候选分子标志物进行生物学功能研究。结果发现，IPO-38、胃泌素、IL-33以及循环血中的FAM5C和MYLK高甲基化等胃癌血清诊断学标志物可作为胃癌早期诊断的标志物。研究还发现，FRZB、TXNL2、PHF10、MPS-1、PTP1B在胃癌组织中均呈高表达，与肿瘤细胞的增殖、分化、凋亡和侵袭等有关；胃癌细胞中AE1高表达可以将p16扣押在胞质，阻止其入核而起到原癌基因的作用；IRX1和miR-126在胃癌组织中均呈低表达，在胃癌中的作用类似抑癌基因。该研究为筛选胃癌候选标志物、开发诊断、分子靶点和预后判断等临床转化研究奠定了良好的基础，并荣获2008年国家科技进步二等奖和2012年上海市科技进步一等奖。

关键词: 胃癌, 分子标志物, 诊断, 治疗, 预后, 转化研究

Abstract:

With high-throughput omics techniques, the gastric cancer-related molecular markers were screened, and the biological functions of candidate gastric cancer molecular markers were studied. The results indicated that IPO-38, gastrin, IL-33, and FAM5C and MYLK methylation in circulation might serve as markers for early diagnosis of gastric cancer. It was also revealed that FRZB, TXNL2, PHF10, MPS-1 and PTP1B were highly expressed in tissues of gastric cancer, which was associated with the proliferation, differentiation, apoptosis and invasion of tumor cells. The high expression of AE1 in gastric cells might keep p16 in cytoplasm, and refrain it from entering nuclei, which served as proto-oncogene. IRX1 and miR-126 were weakly expressed in tissues of gastric cancer, which served as anti-oncogene. The research lays a good foundation for the clinical translational research of screening of candidate gastric cancer markers, development of diagnostics, molecular targets for therapeutics and prognosis prediction. The research findings have won the second prize of National Science Progress in 2008 and first prize of Shanghai Science Progress in 2012.

Key words: gastric cancer, molecular biomarkers, diagnosis, therapy, prognosis, translational research