Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/17661
Title: Colorectal Cancer Cell Line Proteomes Are Representative of Primary Tumors and Predict Drug Sensitivity.
Authors: Wang, Jing;Mouradov, Dmitri;Wang, Xiaojing;Jorissen, Robert N;Chambers, Matthew C;Zimmerman, Lisa J;Vasaikar, Suhas;Love, Christopher G;Li, Shan;Lowes, Kym;Leuchowius, Karl-Johan;Jousset, Helene;Weinstock, Janet;Yau, Christopher;Mariadason, John;Shi, Zhiao;Ban, Yuguang;Chen, Xi;Coffey, Robert J C;Slebos, Robbert J C;Burgess, Antony W;Liebler, Daniel C;Zhang, Bing;Sieber, Oliver M
Affiliation: Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
Department of Biochemistry, Vanderbilt University, Nashville, Tennessee
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
Structural Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
Department of Statistics, University of Oxford, Oxford, United Kingdom
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
La Trobe University School of Cancer Medicine, Melbourne, VIC, Australia
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
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
Veterans Affairs Medical Center, Nashville, Tennessee
Clinical Science Lab, Moffitt Cancer Center, Tampa, Florida
Department of Surgery, The University of Melbourne, Parkville, VIC, Australia
School of Biomedical Sciences, Monash University, Clayton, VIC, Australia
Issue Date: Oct-2017
EDate: 2017-01-16
Citation: Gastroenterology 2017; 153(4): 1082-1095
Abstract: 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.
URI: http://ahro.austin.org.au/austinjspui/handle/1/17661
DOI: 10.1053/j.gastro.2017.06.008
PubMed URL: 28625833
Type: Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Subjects: Cell Lines
Colorectal Cancer
Drug Sensitivity
Proteomics
Appears in Collections:Journal articles

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