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我国科学家提出:蛋白质组可用于早期肝细胞癌的分型、预后和靶向治疗

2019-02-28 22:37:00    新华网

新华社北京2月28日电(记者李斌、胡喆)我国科学家关于早期肝细胞癌蛋白质组研究的论文北京时间2月28日在国际权威期刊《自然》杂志上线发表,文章首次表明蛋白质组可用于早期肝细胞癌的分型、预后和靶向治疗。

科学家根据101例早期肝细胞癌及配对癌旁组织样本的蛋白质组数据,研究团队将以往临床上认为相似的早期肝细胞癌患者分成三种蛋白质组亚型(S-I, S-II, S-III),并证明亚型间表现出非常不同的预后。

研究人员在预后最差的S-III亚型蛋白质组数据里,发现胆固醇代谢发生了重编程,通过抑制候选药靶——胆固醇酯化酶SOAT1,能减少细胞质膜上的胆固醇水平,有效抑制肿瘤细胞的增殖和迁移。

他们进一步研究发现,SOAT1的一种小分子抑制剂“阿伐麦布”在肝癌患者的人源肿瘤异种移植模型上表现出良好的抗肿瘤效果,表明“阿伐麦布”有望成为治疗预后较差肝细胞癌患者的潜在靶向治疗药物。

研究团队借助患者群蛋白质组学海量数据发现胆固醇酯化酶可用于早期肝癌的分型、预后及靶向治疗,其蛋白质水平在头颈癌、胃癌、前列腺癌、肾癌和甲状腺癌中均和患者的较差预后正相关。

蛋白质组是人体表型的直接物质基础。中国是国际蛋白质组计划的重要参与方,也是人类肝脏蛋白质组计划的牵头实施方。2014年,科技部启动“中国人类蛋白质组计划”,迄今已构建早期肝细胞癌、弥漫性胃癌及癌旁组织等十余种疾病组织的深度覆盖蛋白质表达谱,国家大科学设施凤凰工程为此提供了强大支撑。

据了解,这项研究是在科技部支持下,由军事科学院军事医学研究院生命组学研究所贺福初院士和钱小红教授团队,联合复旦大学附属中山医院樊嘉院士、北京大学肿瘤医院邢宝才教授共同完成的。

2018年全球肿瘤统计数据显示,肝癌致死率居恶性肿瘤第二位。手术治疗仅对部分早期肝癌有效,而预后较差的那部分如何识别及其靶向治疗均为当下难题。

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