A novel gene expression signature in peripheral blood mononuclear cells for early detection of colorectal cancer

Summary Background Early detection and treatment of colorectal adenomatous polyps (AP) and colorectal cancer (CRC) is associated with decreased mortality for CRC. However, accurate, non‐invasive and compliant tests to screen for AP and early stages of CRC are not yet available. A blood‐based screening test is highly attractive due to limited invasiveness and high acceptance rate among patients. Aim To demonstrate whether gene expression signatures in the peripheral blood mononuclear cells (PBMC) were able to detect the presence of AP and early stages CRC. Methods A total of 85 PBMC samples derived from colonoscopy‐verified subjects without lesion (controls) (n = 41), with AP (n = 21) or with CRC (n = 23) were used as training sets. A 42‐gene panel for CRC and AP discrimination, including genes identified by Digital Gene Expression‐tag profiling of PBMC, and genes previously characterised and reported in the literature, was validated on the training set by qPCR. Logistic regression analysis followed by bootstrap validation determined CRC‐ and AP‐specific classifiers, which discriminate patients with CRC and AP from controls. Results The CRC and AP classifiers were able to detect CRC with a sensitivity of 78% and AP with a sensitivity of 46% respectively. Both classifiers had a specificity of 92% with very low false‐positive detection when applied on subjects with inflammatory bowel disease (n = 23) or tumours other than CRC (n = 14). Conclusion This pilot study demonstrates the potential of developing a minimally invasive, accurate test to screen patients at average risk for colorectal cancer, based on gene expression analysis of peripheral blood mononuclear cells obtained from a simple blood sample.