Cancer Cell
Volume 38, Issue 5, 9 November 2020, Pages 734-747.e9
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Article
Integrated Omics of Metastatic Colorectal Cancer

https://doi.org/10.1016/j.ccell.2020.08.002Get rights and content
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Highlights

  • A large-scale proteogenomics study of metastatic colorectal cancers

  • Phosphoproteomic pattern distinguishes metastasis and predicts drug response

  • A workflow from generation of large omics datasets to in vivo drug testing models

  • Improves the selection of treatment strategies for patients without druggable mutation

Summary

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.

Keywords

proteogenomic
metastasis
colorectal cancer
phosphorylation
drug testing model

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These authors contributed equally

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