N-myristoyltransferase 2: A novel marker for colorectal cancer screening.

Abstract

e15114 Background: Colorectal cancer (CRC) is the second most common cause of cancer related deaths in North America. Most CRCs arise from pre-malignant adenomatous polyps with some of these polyps developing into cancer over years providing an ideal opportunity for detection and intervention. However, the unpleasant nature of the current screening methods often leads to non-compliance. N-Myristoyltransferase (NMT) has been reported to be overexpressed in CRC tissues. In this study we show that NMT2, an isoform of NMT, is overexpressed in peripheral blood mononuclear cells (PBMC) of individuals with colorectal adenomatous polyps or cancers compared to healthy controls. Methods: PBMC’s were isolated from blood samples of CRC patients (n = 14), individuals with - non-adenomatous polyps (n = 8); adenomatous polyps (n = 18) and healthy controls (n = 24). Immunohistochemistry (IHC) was used to determine the NMT2 expression in these samples. IHC-scores were derived from assessment of both staining intensity (scale 0-3) and percentage of positive cells (0-100%), which were multiplied to generate an IHC -score between 0-300. Observers calculating the IHC scores were unaware of the polyp/CRC status. A receiver operating characteristic (ROC) analysis was performed to assess the overall performance of the NMT2 test via the area under the curve (AUC). Results: NMT2 was significantly overexpressed in PBMC of CRC patients (median IHC score- 196) compared to control subjects (median IHC score- 50). In addition, IHC scores were significantly higher for adenomatous polyps (median IHC score- 165) compared to those with non-adenomatous polyps (median IHC score- 54.8). We included non-adenomatous polyps and healthy subjects in “controls” and adenomatous polyps in “cases” along with CRC in the ROC analysis. The ROC curve of NMT2 expression displayed substantial separation between controls/non adenomatous polyps compared to CRC/adenomatous polyps [AUC = 0.913 (95% CI: 0.830-0.994)]. Conclusions: Our results show an increase in NMT2 expression in PBMC of CRC patients and individuals with adenomatous polyps suggesting that NMT2 could be used as a novel blood based biomarker for the screening and early detection of CRC. Validation studies are the next step.