Assessment of serum proteomics to detect large colon adenomas

Abstract

A noninvasive blood test that could reliably detect early colorectal cancer or large adenomas would provide an important advance in colon cancer screening. The purpose of this study was to determine whether a serum proteomics assay could discriminate between persons with and without a large (≥1 cm) colon adenoma. To avoid problems of "bias" that have affected many studies about molecular markers for diagnosis, specimens were obtained from a previously conducted study of colorectal cancer etiology in which bloods had been collected before the presence or absence of neoplasm had been determined by colonoscopy, helping to assure that biases related to differences in sample collection and handling would be avoided. Mass spectra of 65 unblinded serumsam ples were acquired using a nanoelectrospray ionization source on a QSTAR-XL mass spectrometer. Classification patterns were developed using the ProteomeQuest® algorithm, performing measurements twice on each specimen, and then applied to a blinded validation set of 70 specimens. After removing 33 specimens that had discordant results, the "test group" comprised 37 specimens that had never been used in training. Although in the primary analysis, no discrimination was found, a single post hoc analysis, done after hemolyzed specimens had been removed, showed a sensitivity of 78%, a specificity of 53%, and an accuracy of 63% (95% confidence interval, 53-72%). The results of this study, although preliminary, suggest that further study of serumpr oteomics, in a larger number of appropriate specimens, could be useful. They also highlight the importance of understanding sources of "noise" and "bias" in studies of proteomics assays. Copyright © 2008 American Association for Cancer Research.