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. 2023 Sep 1;32(9):1146-1152.
doi: 10.1158/1055-9965.EPI-22-1020.

Elevated EVL Methylation Level in the Normal Colon Mucosa Is a Potential Risk Biomarker for Developing Recurrent Adenomas

Ming Yu  1 , Kelly T Carter  1 , Kelsey K Baker  1 , Mary W Redman  1 , Ting Wang  1 , Kathy Vickers  2 , Christopher I Li  2   3 , Stacey A Cohen  1   3 , Mukta Krane  3 , Jennifer Ose  4   5 , Biljana Gigic  6 , Jane C Figueiredo  7 , Adetunji T Toriola  8 , Erin M Siegel  9 , David Shibata  10 , Martin Schneider  6 , Cornelia M Ulrich  4   5 , Lynda A Dzubinski  11 , Robert E Schoen  11 , William M Grady  1   3
Affiliations

Elevated EVL Methylation Level in the Normal Colon Mucosa Is a Potential Risk Biomarker for Developing Recurrent Adenomas

Ming Yu et al. Cancer Epidemiol Biomarkers Prev. .

Abstract

Background: Individuals with adenomatous colorectal polyps undergo repeated colonoscopy surveillance to identify and remove metachronous adenomas. However, many patients with adenomas do not develop recurrent adenomas. Better methods to evaluate who benefits from increased surveillance are needed. We evaluated the use of altered EVL methylation as a potential biomarker for risk of recurrent adenomas.

Methods: Patients with ≥1 colonoscopy had EVL methylation (mEVL) measured with an ultra-accurate methylation-specific droplet digital PCR assay on normal colon mucosa. The association between EVL methylation levels and adenoma or colorectal cancer was evaluated using three case/control definitions in three models: unadjusted (model 1), adjusting for baseline characteristics (model 2), and an adjusted model excluding patients with colorectal cancer at baseline (model 3).

Results: Between 2001 and 2020, 136 patients were included; 74 healthy patients and 62 patients with a history of colorectal cancer. Older age, never smoking, and baseline colorectal cancer were associated with higher levels of mEVL (P ≤ 0.05). Each log base 10 difference in mEVL was associated with an increased risk of adenoma(s) or cancer at/after baseline for model 1 [OR, 2.64; 95% confidence interval (CI), 1.09-6.36], and adenoma(s) or cancer after baseline for models 1 (OR, 2.01; 95% CI, 1.04-3.90) and model 2 (OR, 3.17; 95% CI, 1.30-7.72).

Conclusions: Our results suggest that EVL methylation level detected in the normal colon mucosa has the potential to be a biomarker for monitoring the risk for recurrent adenomas.

Impact: These findings support the potential utility of EVL methylation for improving the accuracy for assigning risk for recurrent colorectal adenomas and cancer.

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Conflict of interest statement

Conflict of Interest and Financial Disclosure Statements: W. M. Grady is an advisory board member for Freenome, Guardant Health, and SEngine and consultant for DiaCarta, Natera, Helio, Guidepoint and GLG. He is an investigator in a clinical trial sponsored by Janssen Pharmaceuticals and receives research support from Tempus and LucidDx. R.E. Schoen receives research support from Freenome, Exact Sciences, and Immunovia. C.M. Ulrich has as cancer director oversight over research funded by several pharmaceutical companies but has not received funding directly herself.

Figures

Figure 1:
Figure 1:
Diagram of patients included in the different comparison group analyses described in the Methods and Results sections. One hundred and thirty-six subjects were assessed and compared in Comparison Groups 1–3 as shown.
Figure 2:
Figure 2:
Graphical representation of patient information on timing and outcome of colonoscopies for patients included in the three sets of comparisons. (A) Comparison Set 1: any adenoma(s) or cancer ever vs. no adenoma(s) or cancer ever (B) Comparison Set 2: adenoma(s) or cancer(s) detected at follow up vs. no adenoma(s) at follow up; (C) Comparison Set 3: adenoma(s) or cancer(s) detected at follow up vs. no adenoma(s) at least 4 years of follow up. Each row represents one patient, and each rectangle represents a colonoscopy examination. The colonoscopy timing, results of the colonoscopies, and timing of the biopsies are shown. The side panel displays a heatmap of the EVL methylation levels for each patient. Green: no adenoma(s) detected; Red: adenoma(s); White: no colonoscopy at timepoint; * indicates timepoint tissue biopsy was taken for DNA extraction and EVL methylation measurement.
See this image and copyright information in PMC

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