新研究揭示轉移性結直腸癌的多組學圖譜
作者：
小柯機器人發布時間：2020/9/4 20:11:59
中國科學院分子細胞卓越創新中心曾嶸、吳家瑞以及上海長海醫院張衛研究組合作的最新研究揭示了轉移性結直腸癌（CRC）的多組學圖譜。這一研究成果在線發表在2020年9月3日的《癌細胞》上。
研究人員對146例中國CRC患者的480個臨床組織樣本進行了基因組學、蛋白質組學和蛋白質磷酸化組學的綜合分析，其中70例為轉移性CRC（mCRC）。蛋白質組學可區分三種CRC亞型，其特徵是具有不同的臨床預後和分子特徵。對原發腫瘤單獨進行蛋白質組學和磷酸化蛋白質組學分析可以成功地區分轉移灶。
轉移組織在遺傳學上與原發性腫瘤具有高度的相似性，但在蛋白質組學水平上卻沒有，並且激酶網絡分析顯示原發性結直腸腫瘤與其肝轉移之間存在顯著的異質性。對31種原發性和轉移性腫瘤的體內異種移植物進行藥物測試表明其具有個體化反應，這也可以通過激酶-底物網絡分析來預測，無論腫瘤是否含有靶向藥物針對的基因突變。該研究為更好地了解mCRC提供了寶貴的資源，並具有臨床應用潛力。
附：英文原文
Title: Integrated Omics of Metastatic Colorectal Cancer
Author: Chen Li, Yi-Di Sun, Guan-Yu Yu, Jing-Ru Cui, Zheng Lou, Hang Zhang, Ya Huang, Chen-Guang Bai, Lu-Lu Deng, Peng Liu, Kuo Zheng, Yan-Hua Wang, Qin-Qin Wang, Qing-Run Li, Qing-Qing Wu, Qi Liu, Yu Shyr, Yi-Xue Li, Luo-Nan Chen, Jia-Rui Wu, Wei Zhang, Rong Zeng
Issue&Volume: 2020-09-03
Abstract: We integrate the genomics, proteomics, and phosphoproteomics of 480 clinical tissuesfrom 146 patients in a Chinese colorectal cancer (CRC) cohort, among which 70 hadmetastatic CRC (mCRC). Proteomic profiling differentiates three CRC subtypes characterizedby distinct clinical prognosis and molecular signatures. Proteomic and phosphoproteomicprofiling of primary tumors alone successfully distinguishes cases with metastasis.Metastatic tissues exhibit high similarities with primary tumors at the genetic butnot the proteomic level, and kinase network analysis reveals significant heterogeneitybetween primary colorectal tumors and their liver metastases. In vivo xenograft-based drug tests using 31 primary and metastatic tumors show personalizedresponses, which could also be predicted by kinase-substrate network analysis no matterwhether tumors carry mutations in the drug-targeted genes. Our study provides a valuableresource for better understanding of mCRC and has potential for clinical application.
DOI: 10.1016/j.ccell.2020.08.002
Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(20)30413-X