A multiplex serum protein assay for determining the probability of colorectal cancer.

Our purpose is to develop a serum assay to determine an individual's probability of having colorectal cancer (CRC). We have discovered a protein panel yielding encouraging, clinically significant results. We evaluated 431 serum samples from donors screened for CRC by colonoscopy. We compared the concentration of seven proteins in individuals with CRC versus individuals found to be CRC free. The assay monitored a single peptide from each of seven proteins. Comparing CRC to normal samples in univariate two-sample t-tests, 6 of the 7 proteins yielded a p-value less than 0.01. Logistic regression was used to construct a model for determination of CRC probability. The model was fit on a randomly chosen training set of 321 samples. Using 6 of the 7 proteins (ORM1, GSN, C9, HABP2, SAA2, and C3) and a cut point of 0.4, an independent test set of 110 samples yielded a sensitivity of 93.75%, a specificity of 82.89% and a prevalence-adjusted negative predictive value (NPV) of 99.9775% for the assay. The results demonstrate that the assay has promise as a sensitive, non-invasive diagnostic test to provide individuals with an understanding of their own probability of having CRC.