PCG相关蛋白RYBP在肝细胞癌发病和预后中的分子流行病学研究

项目名称： PCG相关蛋白RYBP在肝细胞癌发病和预后中的分子流行病学研究

项目编号： No.81460515

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 谭盛葵

作者单位： 桂林医学院

项目金额： 55万元

中文摘要： 肝癌是广西南部高发的恶性肿瘤，其高侵袭性、高转移复发性，往往是制约其整体疗效的关键。RYBP是新近识别的多梳蛋白(PcG)家族成员，除参与PcG抑制复合物组成和抑制转录功能外，与细胞增殖和凋亡密切相关，可能具有抑制肿瘤侵袭转移的作用。在国家自然科学基金的基础上，我们初步检测了50对肝癌手术患者的冻存癌和癌旁组织，发现86%的样本癌组织中RYBP表达明显低于癌旁组织，其表达水平与肝癌转移有关，且患者的生存时间随表达水平的升高而呈明显延长趋势。利用前期工作积累，本项目拟对肝癌手术存活患者进行前瞻性随访，采用大规模临床肝癌样本的关联研究结合体内外实验方法，进一步验证RYBP基因表达缺失或下调在肝癌发病和预后中的作用，探讨RYBP表达变化对肝癌细胞生物学特性的影响,初步研究RYBP参与EMT影响肝癌侵袭转移的分子调控机制，为筛选肝癌易感人群及临床判断预后提供参考，为寻找肝癌潜在的诊治靶标提供依据。

中文关键词： RYBP；肝细胞癌；前瞻性随访；分子流行病学；PCG相关蛋白

英文摘要： Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in southern Guangxi. High invasion, metastasis and recurrence contribute much to the poor prognosis of HCC. RYBP is a newly identified member of polycomb group (PcG) family participating in composition of PcG repressor complex and inhibiting transcription as well as involved in cell proliferation and apoptosis，which may play a role in invasion and metastasis. Funded by Natural Science Foundation of China, we have discovered by previous works that RYBP expression decreases significantly in 86％ cancer tissue samples compared to adjacent noncancerous tissue samples, FOXO4 expression level is related to tumor metastasis, and HCC patients with FOXO4 expression rising gradually have obviously prolonged lifespan by preliminarily detecting 50 pairs cryopreserved carcinoma and adjacent noncancerous tissues of HCC patients after curative resection. This project prepares to make prospective follow-up of survival HCC patients after curative resection. Large-scale clinical HCC samples combining with vitro&vivo experiment are conducted to validate the role of RYBP expression loss or down-regulation playing in HCC pathogenesis and prognosis, investigate the influences on HCC cells biological characteristics with RYBP expression changing, and primarily study the molecular regulation mechanisms of RYBP that participates in EMT in HCC invasion and metastasis , so as to provide reference for screening of HCC susceptible population and judging clinical prognosis and provide evidence for searching potential targets of HCC diagnosis and treatment.

英文关键词： RYBP;Hepatocellular carcinoma;Prospective follow-up;Molecular epidemiology;PCG-associated proteins