Author:
Ivancic Melanie M.,Anson Leigh W.,Pickhardt Perry J.,Megna Bryant,Pooler Bryan D.,Clipson Linda,Reichelderfer Mark,Sussman Michael R.,Dove William F.
Abstract
A major challenge for the reduction of colon cancer is to detect patients carrying high-risk premalignant adenomas with minimally invasive testing. As one step, we have addressed the feasibility of detecting protein signals in the serum of patients carrying an adenoma as small as 6–9 mm in maximum linear dimension. Serum protein biomarkers, discovered in two animal models of early colonic adenomagenesis, were studied in patients using quantitative mass-spectrometric assays. One cohort included patients bearing adenomas known to be growing on the basis of longitudinal computed tomographic colonography. The other cohort, screened by optical colonoscopy, included both patients free of adenomas and patients bearing adenomas whose risk status was judged by histopathology. The markers F5, ITIH4, LRG1, and VTN were each elevated both in this patient study and in the studies of the Pirc rat model. The quantitative study in the Pirc rat model had demonstrated that the elevated level of each of these markers is correlated with the number of colonic adenomas. However, the levels of these markers in patients were not significantly correlated with the total adenoma volume. Postpolypectomy blood samples demonstrated that the elevated levels of these four conserved markers persisted after polypectomy. Two additional serum markers rapidly renormalized after polypectomy: growth-associated CRP levels were enhanced only with high-risk adenomas, while PI16 levels, not associated with growth, were reduced regardless of risk status. We discuss biological hypotheses to account for these observations, and ways for these signals to contribute to the prevention of colon cancer.
Funder
HHS | NIH | National Center for Advancing Translational Sciences
Wisconsin Alumni Research Foundation
HHS | National Institutes of Health
SciMed Graduate Research Scholars
University of Wisconsin School of Medicine and Public Health Shapiro Research Program
Publisher
Proceedings of the National Academy of Sciences
Cited by
13 articles.
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