N-myristoyltransferase 2-based Blood Test for the Detection of Colorectal Adenomatous Polyps and Cancer

Tharmini Rathinagopal; Shiv Bhanot; Sergey Yegrov; Jordan Min; Nan Hu; John Fang; Tom H Greene; Shailly Varma Shrivastav; Harminder Singh; Anuraag Shrivastav

doi:10.1097/AS9.0000000000000117

N-myristoyltransferase 2-based Blood Test for the Detection of Colorectal Adenomatous Polyps and Cancer

Ann Surg Open. 2022 Jan 7;3(1):e117. doi: 10.1097/AS9.0000000000000117. eCollection 2022 Mar.

Authors

Tharmini Rathinagopal^{1

2}, Shiv Bhanot², Sergey Yegrov¹, Jordan Min¹, Nan Hu³, John Fang⁴, Tom H Greene³, Shailly Varma Shrivastav¹, Harminder Singh^{5

6}, Anuraag Shrivastav^{2

6}

Affiliations

¹ From the VastCon Inc, Winnipeg, MB, Canada.
² Department of Biology, University of Winnipeg, Winnipeg, MB, Canada.
³ Division of Biostatistics, University of Utah, Salt Lake City, UT.
⁴ Division of Gastroenterology, School of Medicine, University of Utah, Salt Lake City, UT.
⁵ Departments of Internal Medicine and Community Health Sciences, College of Medicine, University of Manitoba, Winnipeg, MB, Canada.
⁶ CancerCare Manitoba Research Institute, Winnipeg, Canada. Winnipeg, MB, Canada.

Abstract

Background: Colorectal cancer is the second leading cause of cancer-related deaths. This study demonstrates the utility of a simple blood test with high sensitivity and specificity for colorectal adenomatous polyps and cancer. A simple blood test with high sensitivity and specificity for adenomas would help identify individuals for a follow-up colonoscopy during which any adenomatous polyps found could be removed, thus preventing colorectal cancer (CRC).

Methods: We determined the H-score by using immunohistochemical analyses of N-myristoyltransferase 2 (NMT2) in peripheral blood mononuclear cells (PBMC) isolated from the blood. We determined the sensitivity and specificity of the NMT2-based blood test in identifying colorectal adenomatous polyps and cancer.

Design: All experimental procedures were performed by research personnel blinded to the colonoscopy status of the participants.

Setting: In this cohort study, participants were recruited from those coming for an outpatient colonoscopy at a referral center.

Participants: PBMC were collected from 74 subjects at the Health Sciences Centre, Winnipeg, Canada. Samples were collected from colonoscopy patients prior to colonoscopy. All 74 subjects were included in CRC vs. non-CRC analysis, whereas only 70 subjects were analyzed for colorectal adenomatous polyps and cancer versus individuals with no evidence of disease and non-adenomatous polyps. NMT2 expression was tested in samples by immunohistochemistry.

Results: The expression of NMT2 was significantly higher in PBMC of subjects with colorectal adenomatous polyps and cancer (n = 34) compared with individuals with non-adenomatous polyps or no evidence of disease (n = 36) (P < 0.0001). The test had an overall sensitivity of 91% (95% confidence intervals: 84.49-97.80) and specificity of 81% (95% confidence intervals: 71.28-89.83) in detecting colorectal adenomatous polyps and cancer (all stages).

Conclusions: Our results suggest that the sensitivity of NMT2 in detecting adenomatous polyps is high (91%). A simple blood-based CRC screening test using NMT2 expression detects colorectal adenomatous polyps and cancer with high sensitivity and specificity has the potential of increasing the compliance for CRC screening as has been reported for other blood-based CRC screening tests.

Keywords: N-myristoltransferase 2; PBMC; adenomatous polyps; colorectal cancer.