Colorectal Cancer Cell Line Proteomes Are Representative of Primary Tumors and Predict Drug Sensitivity

Jing Wang; Dmitri Mouradov; Xiaojing Wang; Robert N Jorissen; Matthew C Chambers; Lisa J Zimmerman; Suhas Vasaikar; Christopher G Love; Shan Li; Kym Lowes; Karl-Johan Leuchowius; Helene Jousset; Janet Weinstock; Christopher Yau; John Mariadason; Zhiao Shi; Yuguang Ban; Xi Chen; Robert J C Coffey; Robbert J C Slebos; Antony W Burgess; Daniel C Liebler; Bing Zhang; Oliver M Sieber

doi:10.1053/j.gastro.2017.06.008

Back

Colorectal Cancer Cell Line Proteomes Are Representative of Primary Tumors and Predict Drug Sensitivity

Journal article

Open access

Peer reviewed

Colorectal Cancer Cell Line Proteomes Are Representative of Primary Tumors and Predict Drug Sensitivity

Jing Wang, Dmitri Mouradov, Xiaojing Wang, Robert N Jorissen, Matthew C Chambers, Lisa J Zimmerman, Suhas Vasaikar, Christopher G Love, Shan Li, Kym Lowes, …

Gastroenterology (New York, N.Y. 1943), Vol.153(4), pp.1082-1095

2017-10

DOI: https://doi.org/10.1053/j.gastro.2017.06.008

PMCID: PMC5623120

PMID: 28625833

Abstract

Colorectal Neoplasms - genetics

Humans

Gene Expression Regulation, Neoplastic

Transcriptome

Tumor Microenvironment

Gene Expression Profiling

Neoplasm Proteins - metabolism

Patient Selection

Dose-Response Relationship, Drug

Tandem Mass Spectrometry

Colorectal Neoplasms - drug therapy

Databases, Protein

Biomarkers, Tumor - metabolism

Chromatography, Liquid

Antineoplastic Agents - pharmacology

Proteomics - methods

Neoplasm Proteins - genetics

Colorectal Neoplasms - metabolism

Precision Medicine

Stromal Cells - metabolism

Proteome

Cell Line, Tumor

Biomarkers, Tumor - genetics

Polymorphism, Single Nucleotide

Colorectal Neoplasms - pathology

Drug Screening Assays, Antitumor

Signal Transduction

Mutation

Proteomics holds promise for individualizing cancer treatment. We analyzed to what extent the proteomic landscape of human colorectal cancer (CRC) is maintained in established CRC cell lines and the utility of proteomics for predicting therapeutic responses. Proteomic and transcriptomic analyses were performed on 44 CRC cell lines, compared against primary CRCs (n=95) and normal tissues (n=60), and integrated with genomic and drug sensitivity data. Cell lines mirrored the proteomic aberrations of primary tumors, in particular for intrinsic programs. Tumor relationships of protein expression with DNA copy number aberrations and signatures of post-transcriptional regulation were recapitulated in cell lines. The 5 proteomic subtypes previously identified in tumors were represented among cell lines. Nonetheless, systematic differences between cell line and tumor proteomes were apparent, attributable to stroma, extrinsic signaling, and growth conditions. Contribution of tumor stroma obscured signatures of DNA mismatch repair identified in cell lines with a hypermutation phenotype. Global proteomic data showed improved utility for predicting both known drug-target relationships and overall drug sensitivity as compared with genomic or transcriptomic measurements. Inhibition of targetable proteins associated with drug responses further identified corresponding synergistic or antagonistic drug combinations. Our data provide evidence for CRC proteomic subtype-specific drug responses. Proteomes of established CRC cell line are representative of primary tumors. Proteomic data tend to exhibit improved prediction of drug sensitivity as compared with genomic and transcriptomic profiles. Our integrative proteogenomic analysis highlights the potential of proteome profiling to inform personalized cancer medicine.

Files and links (1)

url

https://doi.org/10.1053/j.gastro.2017.06.008View

Published (Version of record) Open

Metrics

7 Record Views

49 Times Cited - Web of Science

InCites Highlights

These are selected metrics from InCites Benchmarking & Analytics tool, related to this output

Collaboration types: Domestic collaboration; International collaboration
Citation topics: 2 Chemistry; 2.211 Mass Spectrometry; 2.211.497 Proteomics
Web Of Science research areas: Gastroenterology & Hepatology
ESI research areas: Clinical Medicine

UN Sustainable Development Goals (SDGs)

This output has contributed to the advancement of the following goals:

Source: InCites

Details

Title: Colorectal Cancer Cell Line Proteomes Are Representative of Primary Tumors and Predict Drug Sensitivity
Creators: Jing Wang - Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
Dmitri Mouradov - Systems Biology and Personalised Medicine Division, The Walter and Eliza Hall Institute of Medial Research, Parkville, VIC, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia
Xiaojing Wang - Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
Robert N Jorissen - Systems Biology and Personalised Medicine Division, The Walter and Eliza Hall Institute of Medial Research, Parkville, VIC, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia
Matthew C Chambers - Department of Biochemistry, Vanderbilt University, Nashville, Tennessee
Lisa J Zimmerman - Department of Biochemistry, Vanderbilt University, Nashville, Tennessee
Suhas Vasaikar - Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
Christopher G Love - Systems Biology and Personalised Medicine Division, The Walter and Eliza Hall Institute of Medial Research, Parkville, VIC, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia
Shan Li - Systems Biology and Personalised Medicine Division, The Walter and Eliza Hall Institute of Medial Research, Parkville, VIC, Australia
Kym Lowes - Systems Biology and Personalised Medicine Division, The Walter and Eliza Hall Institute of Medial Research, Parkville, VIC, Australia
Karl-Johan Leuchowius - Systems Biology and Personalised Medicine Division, The Walter and Eliza Hall Institute of Medial Research, Parkville, VIC, Australia
Helene Jousset - Systems Biology and Personalised Medicine Division, The Walter and Eliza Hall Institute of Medial Research, Parkville, VIC, Australia
Janet Weinstock - Structural Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
Christopher Yau - Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Department of Statistics, University of Oxford, Oxford, United Kingdom
John Mariadason - Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, Australia; La Trobe University School of Cancer Medicine, Melbourne, VIC, Australia
Zhiao Shi - Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas
Yuguang Ban - Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida
Xi Chen - Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida; Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, Florida
Robert J C Coffey - Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee; Veterans Affairs Medical Center, Nashville, Tennessee
Robbert J C Slebos - Clinical Science Lab, Moffitt Cancer Center, Tampa, Florida
Antony W Burgess - Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia; Structural Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Surgery, The University of Melbourne, Parkville, VIC, Australia
Daniel C Liebler - Department of Biochemistry, Vanderbilt University, Nashville, Tennessee
Bing Zhang - Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas. Electronic address: bing.zhang@bcm.edu
Oliver M Sieber - Systems Biology and Personalised Medicine Division, The Walter and Eliza Hall Institute of Medial Research, Parkville, VIC, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia; Department of Surgery, The University of Melbourne, Parkville, VIC, Australia; School of Biomedical Sciences, Monash University, Clayton, VIC, Australia. Electronic address: sieber.o@wehi.edu.au
Publication Details: Gastroenterology (New York, N.Y. 1943), Vol.153(4), pp.1082-1095
Publisher: United States
Grant note: U24 CA159988 / NCI NIH HHS U24 CA210954 / NCI NIH HHS P50 CA095103 / NCI NIH HHS R01 CA151566 / NCI NIH HHS R01 CA046413 / NCI NIH HHS R35 CA197570 / NCI NIH HHS
Academic Unit: Miller School of Medicine; UMMG Department of Public Health Sciences Research
Language: English
Resource Type: Journal article
PMID: 28625833
PMCID: PMC5623120
Record Identifier: 991031578495702976