Open AccessPharmacoproteomic characterisation of human colon and rectal cancer
Author(s) -
Frejno Martin,
Zenezini Chiozzi Riccardo,
Wilhelm Mathias,
Koch Heiner,
Zheng Runsheng,
Klaeger Susan,
Ruprecht Benjamin,
Meng Chen,
Kramer Karl,
Jarzab Anna,
Heinzlmeir Stephanie,
Johnstone Elaine,
Domingo Enric,
Kerr David,
Jesinghaus Moritz,
SlottaHuspenina Julia,
Weichert Wilko,
Knapp Stefan,
Feller Stephan M,
Kuster Bernhard
Publication year - 2017
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.15252/msb.20177701
Subject(s) - biology , colorectal cancer , computational biology , cancer , cancer research , genetics
Most molecular cancer therapies act on protein targets but data on the proteome status of patients and cellular models for proteome‐guided pre‐clinical drug sensitivity studies are only beginning to emerge. Here, we profiled the proteomes of 65 colorectal cancer ( CRC ) cell lines to a depth of > 10,000 proteins using mass spectrometry. Integration with proteomes of 90 CRC patients and matched transcriptomics data defined integrated CRC subtypes, highlighting cell lines representative of each tumour subtype. Modelling the responses of 52 CRC cell lines to 577 drugs as a function of proteome profiles enabled predicting drug sensitivity for cell lines and patients. Among many novel associations, MERTK was identified as a predictive marker for resistance towards MEK 1/2 inhibitors and immunohistochemistry of 1,074 CRC tumours confirmed MERTK as a prognostic survival marker. We provide the proteomic and pharmacological data as a resource to the community to, for example, facilitate the design of innovative prospective clinical trials.