Pharmacoproteomic characterisation of human colon and rectal cancer
Abstract 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...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2017-11-01
|
| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/msb.20177701 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849738417584209920 |
|---|---|
| author | Martin Frejno Riccardo Zenezini Chiozzi Mathias Wilhelm Heiner Koch Runsheng Zheng Susan Klaeger Benjamin Ruprecht Chen Meng Karl Kramer Anna Jarzab Stephanie Heinzlmeir Elaine Johnstone Enric Domingo David Kerr Moritz Jesinghaus Julia Slotta‐Huspenina Wilko Weichert Stefan Knapp Stephan M Feller Bernhard Kuster |
| author_facet | Martin Frejno Riccardo Zenezini Chiozzi Mathias Wilhelm Heiner Koch Runsheng Zheng Susan Klaeger Benjamin Ruprecht Chen Meng Karl Kramer Anna Jarzab Stephanie Heinzlmeir Elaine Johnstone Enric Domingo David Kerr Moritz Jesinghaus Julia Slotta‐Huspenina Wilko Weichert Stefan Knapp Stephan M Feller Bernhard Kuster |
| author_sort | Martin Frejno |
| collection | DOAJ |
| description | Abstract 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 MEK1/2 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. |
| format | Article |
| id | doaj-art-42fe166316444fdb9fe348ff8da129f1 |
| institution | DOAJ |
| issn | 1744-4292 |
| language | English |
| publishDate | 2017-11-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-42fe166316444fdb9fe348ff8da129f12025-08-20T03:06:36ZengSpringer NatureMolecular Systems Biology1744-42922017-11-01131111510.15252/msb.20177701Pharmacoproteomic characterisation of human colon and rectal cancerMartin Frejno0Riccardo Zenezini Chiozzi1Mathias Wilhelm2Heiner Koch3Runsheng Zheng4Susan Klaeger5Benjamin Ruprecht6Chen Meng7Karl Kramer8Anna Jarzab9Stephanie Heinzlmeir10Elaine Johnstone11Enric Domingo12David Kerr13Moritz Jesinghaus14Julia Slotta‐Huspenina15Wilko Weichert16Stefan Knapp17Stephan M Feller18Bernhard Kuster19Department of Oncology, University of OxfordChair of Proteomics and Bioanalytics, Technical University of MunichChair of Proteomics and Bioanalytics, Technical University of MunichChair of Proteomics and Bioanalytics, Technical University of MunichChair of Proteomics and Bioanalytics, Technical University of MunichChair of Proteomics and Bioanalytics, Technical University of MunichChair of Proteomics and Bioanalytics, Technical University of MunichChair of Proteomics and Bioanalytics, Technical University of MunichChair of Proteomics and Bioanalytics, Technical University of MunichChair of Proteomics and Bioanalytics, Technical University of MunichChair of Proteomics and Bioanalytics, Technical University of MunichDepartment of Oncology, University of OxfordDepartment of Oncology, University of OxfordNuffield Division of Clinical Laboratory Sciences (NDCLS), University of OxfordInstitute of Pathology, Technical University of MunichInstitute of Pathology, Technical University of MunichInstitute of Pathology, Technical University of MunichInstitute of Pharmaceutical Chemistry, Goethe UniversityWeatherall Institute of Molecular Medicine, University of OxfordChair of Proteomics and Bioanalytics, Technical University of MunichAbstract 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 MEK1/2 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.https://doi.org/10.15252/msb.20177701CPTACCRC65drug responsepatient stratificationproteomics |
| spellingShingle | Martin Frejno Riccardo Zenezini Chiozzi Mathias Wilhelm Heiner Koch Runsheng Zheng Susan Klaeger Benjamin Ruprecht Chen Meng Karl Kramer Anna Jarzab Stephanie Heinzlmeir Elaine Johnstone Enric Domingo David Kerr Moritz Jesinghaus Julia Slotta‐Huspenina Wilko Weichert Stefan Knapp Stephan M Feller Bernhard Kuster Pharmacoproteomic characterisation of human colon and rectal cancer Molecular Systems Biology CPTAC CRC65 drug response patient stratification proteomics |
| title | Pharmacoproteomic characterisation of human colon and rectal cancer |
| title_full | Pharmacoproteomic characterisation of human colon and rectal cancer |
| title_fullStr | Pharmacoproteomic characterisation of human colon and rectal cancer |
| title_full_unstemmed | Pharmacoproteomic characterisation of human colon and rectal cancer |
| title_short | Pharmacoproteomic characterisation of human colon and rectal cancer |
| title_sort | pharmacoproteomic characterisation of human colon and rectal cancer |
| topic | CPTAC CRC65 drug response patient stratification proteomics |
| url | https://doi.org/10.15252/msb.20177701 |
| work_keys_str_mv | AT martinfrejno pharmacoproteomiccharacterisationofhumancolonandrectalcancer AT riccardozenezinichiozzi pharmacoproteomiccharacterisationofhumancolonandrectalcancer AT mathiaswilhelm pharmacoproteomiccharacterisationofhumancolonandrectalcancer AT heinerkoch pharmacoproteomiccharacterisationofhumancolonandrectalcancer AT runshengzheng pharmacoproteomiccharacterisationofhumancolonandrectalcancer AT susanklaeger pharmacoproteomiccharacterisationofhumancolonandrectalcancer AT benjaminruprecht pharmacoproteomiccharacterisationofhumancolonandrectalcancer AT chenmeng pharmacoproteomiccharacterisationofhumancolonandrectalcancer AT karlkramer pharmacoproteomiccharacterisationofhumancolonandrectalcancer AT annajarzab pharmacoproteomiccharacterisationofhumancolonandrectalcancer AT stephanieheinzlmeir pharmacoproteomiccharacterisationofhumancolonandrectalcancer AT elainejohnstone pharmacoproteomiccharacterisationofhumancolonandrectalcancer AT enricdomingo pharmacoproteomiccharacterisationofhumancolonandrectalcancer AT davidkerr pharmacoproteomiccharacterisationofhumancolonandrectalcancer AT moritzjesinghaus pharmacoproteomiccharacterisationofhumancolonandrectalcancer AT juliaslottahuspenina pharmacoproteomiccharacterisationofhumancolonandrectalcancer AT wilkoweichert pharmacoproteomiccharacterisationofhumancolonandrectalcancer AT stefanknapp pharmacoproteomiccharacterisationofhumancolonandrectalcancer AT stephanmfeller pharmacoproteomiccharacterisationofhumancolonandrectalcancer AT bernhardkuster pharmacoproteomiccharacterisationofhumancolonandrectalcancer |