title: The concentrations of EGFR, LRG1, ITIH4, and F5 in serum correlate with the number of colonic adenomas in ApcPirc/+ rats.
abstract: The development of noninvasive methods for early detection of colon cancer is critical for the successful management of this disease. Using a targeted quantitative proteomics technique, we assessed the ability of 12 serum proteins to detect the presence of colonic polyps in the Apc(Pirc) (/+) rat model of familial colon cancer. Serum protein candidates were selected from gene transcripts upregulated in colonic tumors of Apc(Pirc) (/+) rats and from a prior study of serum proteins differentially expressed in mice carrying intestinal adenomas. Proteins were quantified at early stages of polyp formation in a rat cohort monitored longitudinally by colonoscopy over a period of 75 days. Of the 12 proteins monitored at three distinct time points, seven showed differential expression in at least one time point in the serum from Apc(Pirc) (/+) rats compared with wild-type rats. Tumor multiplicity correlated with protein expression changes, and most tumors grew during the study. EGFR, LRG1, ITIH4, and F5 displayed the most robust tumor-associated protein expression changes over time. Receiver operator characteristic analysis using these four proteins resulted in a sensitivity of 100%, a specificity of 80%, and an area under the curve of 0.93 at 135 days of age, when the Pirc rats bore an average of 19 tumors in the colon and seven in the small intestine. The results of this study demonstrate that the quantitative analysis of a panel of serum proteins can detect the presence of early intestinal tumors in a rat model, and provides support for future measurements in humans.
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Melanie M
authors.initials: MM
authors.lastname: Ivancic
authors.affiliation: McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, Wisconsin. Molecular and Environmental Toxicology Center, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Amy A
authors.initials: AA
authors.lastname: Irving
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Kelli G
authors.initials: KG
authors.lastname: Jonakin
authors.affiliation: McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, Wisconsin. Department of Oncology, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: William F
authors.initials: WF
authors.lastname: Dove
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin. Biotechnology Center, University of Wisconsin-Madison, Madison, Wisconsin. msussman@wisc.edu.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Sussman
mesh_terms: D000236:Adenoma / Q000378:metabolism; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood; D001798:Blood Proteins / Q000032:analysis*; D002135:Calcium-Binding Proteins / Q000097:blood*; D002853:Chromatography, Liquid; D003110:Colonic Neoplasms / Q000097:blood*; D003113:Colonoscopy; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000097:blood*; D005165:Factor V / Q000032:analysis*; D005189:False Positive Reactions; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000032:analysis / Q000097:blood*; D008297:Male; D013058:Mass Spectrometry; D020411:Oligonucleotide Array Sequence Analysis; D053491:Proteinase Inhibitory Proteins, Secretory; D040901:Proteomics; D012333:RNA, Messenger / Q000378:metabolism; D012372:ROC Curve; D051381:Rats; D011916:Rats, Inbred F344; D055647:Rats, Transgenic
chemical_list: D014408:Biomarkers, Tumor; D001798:Blood Proteins; D002135:Calcium-Binding Proteins; D006023:Glycoproteins; C000599468:ITIH4 protein, rat; C000599467:LRG1 protein, rat; D053491:Proteinase Inhibitory Proteins, Secretory; D012333:RNA, Messenger; D005165:Factor V; C483803:Egfr protein, rat; D066246:ErbB Receptors