Integrated Omics of Metastatic Colorectal Cancer
Integrated Omics of Metastatic Colorectal Cancer
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DOI：
10.1016/j.ccell.2020.08.002
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发表时间：
2020-11-09
期刊：
影响因子：
50.3
通讯作者：
Zeng, Rong
中科院分区：
文献类型：
--
作者：
Li, Chen;Sun, Yi-Di;Zeng, Rong
我们整合了中国结直肠癌（CRC）队列中146例患者的480例临床组织的基因组学、蛋白质组学和磷酸化蛋白质组学，其中70例为转移性CRC（mCRC）。蛋白质组分析区分三种CRC亚型，其特征在于不同的临床预后和分子特征。仅原发肿瘤的蛋白质组学和磷酸化蛋白质组学分析就成功区分了转移病例。转移性组织在基因水平上与原发性肿瘤表现出高度相似性，但在蛋白质组水平上则不然，激酶网络分析揭示了原发性结直肠肿瘤与其肝转移瘤之间的显著异质性。使用31种原发性和转移性肿瘤进行的体内异种移植物药物试验显示出个性化的反应，无论肿瘤是否携带药物靶向基因突变，都可以通过激酶-底物网络分析预测。我们的研究为更好地了解mCRC提供了宝贵的资源，并具有临床应用的潜力。
We integrate the genomics, proteomics, and phosphoproteomics of 480 clinical tissues from 146 patients in a Chinese colorectal cancer (CRC) cohort, among which 70 had metastatic CRC (mCRC). Proteomic profiling differentiates three CRC subtypes characterized by distinct clinical prognosis and molecular signatures. Proteomic and phosphoproteomic profiling of primary tumors alone successfully distinguishes cases with metastasis. Metastatic tissues exhibit high similarities with primary tumors at the genetic but not the proteomic level, and kinase network analysis reveals significant heterogeneity between primary colorectal tumors and their liver metastases. In vivo xenograft-based drug tests using 31 primary and metastatic tumors show personalized responses, which could also be predicted by kinase-substrate network analysis no matter whether tumors carry mutations in the drug-targeted genes. Our study provides a valuable resource for better understanding of mCRC and has potential for clinical application.