蛋白质组学确定了早期肝细胞癌的新治疗点
Ying Jiang1, Aihua Sun1, Yang Zhao1,2
1State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China.
Nature
|March 1, 2019
概括
通过蛋白质分析确定了肝细胞癌 (HCC) 的亚型. 与胆固醇干扰和高SOAT1表达相关的S-III亚型显示出不良预后,但可能对像阿瓦西米布这样的SOAT1抑制剂产生反应.
科学领域:
- 癌症学
- 蛋白质组学
- 分子生物学
背景情况:
- 肝细胞癌 (HCC) 是全球主要的癌症,乙型肝炎病毒 (HBV) 感染是主要的风险因素,特别是在东亚.
- 尽管早期HCC的手术选择,但存活率仍然低于最佳水平,这凸显了更好的预后工具和向治疗的需要.
研究的目的:
- 通过蛋白质组和蛋白质组分析对早期的HBV相关肝细胞癌进行分层.
- 识别不同的分子亚型及其与临床结果的关联.
- 研究醇O-转移酶1 (SOAT1) 在HCC进展和治疗潜力的作用.
主要方法:
- 110个结对的瘤和非瘤HCC组织的蛋白质和光蛋白质分析.
- 用生物信息分析将患者分为亚型 (S-I,S-II,S-III).
- 使用患者衍生的瘤异种移植小鼠模型进行的SOAT1试验和体内试验.
主要成果:
- 蛋白质组数据显示出显著的异质性,使得分层分为三种亚型 (S- I,S- II,S- III),具有不同的临床结果.
- 这种S-III亚型的特征是胆固醇平衡受损,SOAT1表达高,与最差的存活率和术后复发的风险增加相关.
- 在SOAT1高的异体移植中,阿瓦西米布治疗显著降低了瘤大小.
结论:
- 蛋白质分层为早期HBV相关的HCC生物学和异质性提供了新的见解.
- 通过SOAT1抑制向胆固醇代谢的S-III亚型代表了一个高风险群体.
- 这项研究建议基于分子亚型和SOAT1表达的个性化治疗策略.
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