title: Linking patient outcome to high throughput protein expression data identifies novel regulators of colorectal adenocarcinoma aggressiveness.
abstract: A key question in cancer systems biology is how to use molecular data to predict the biological behavior of tumors from individual patients. While genomics data have been heavily used, protein signaling data are more directly connected to biological phenotype and might predict cancer phenotypes such as invasion, metastasis, and patient survival. In this study, we mined publicly available data for colorectal adenocarcinoma from the Cancer Genome Atlas and identified protein expression and signaling changes that are statistically associated with patient outcome. Our analysis identified a number of known and potentially new regulators of colorectal cancer. High levels of insulin growth factor binding protein 2 (IGFBP2) were associated with both recurrence and death, and this was validated by immunohistochemical staining of a tissue microarray for a secondary patient dataset. Interestingly, GATA binding protein 3 (GATA3) was the protein most frequently associated with death in our analysis, and GATA3 expression was significantly decreased in tumor samples from stage I-II deceased patients. Experimental studies using engineered colon cancer cell lines show that exogenous expression of GATA3 decreases three-dimensional colony growth and invasiveness of colon cancer cells but does not affect two-dimensional proliferation. These findings suggest that protein data are useful for biomarker discovery and identify GATA3 as a regulator of colorectal cancer  aggressiveness.
authors.affiliation: Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.
authors.forename: Christi L
authors.initials: CL
authors.lastname: French
authors.affiliation: Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, 37232, USA ; Center for Quantitative Sciences, Vanderbilt University, Nashville, TN, 37232, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Ye
authors.affiliation: Department of Pathology,Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Revetta
authors.affiliation: Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA ; Center for Quantitative Sciences, Vanderbilt University, Nashville, TN, 37232, USA ; Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, 37232, USA ; Vanderbilt Ingram Cancer Center, Nashville, TN, 37232, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA ; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA ; Department of Veterans Affairs Medical Center, Nashville, TN, 37232, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Coffey
authors.affiliation: Department of Pathology,Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
authors.forename: M Kay
authors.initials: MK
authors.lastname: Washington
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
authors.forename: Natasha G
authors.initials: NG
authors.lastname: Deane
authors.affiliation: Vanderbilt Ingram Cancer Center, Nashville, TN, 37232, USA.
authors.forename: R Daniel
authors.initials: RD
authors.lastname: Beauchamp
authors.affiliation: Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA ; Department of Pathology,Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA ; Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA ; Vanderbilt Ingram Cancer Center, Nashville, TN, 37232, USA.
authors.forename: Alissa M
authors.initials: AM
authors.lastname: Weaver
keywords: Bioinformatics; Cancer Biology; Colorectal Cancer; Prognosis; Proteomics; Reverse Phase Protein Array; TCGA