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Updated: May 11, 2025
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Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
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Methylated Reprimo Cell-Free DNA as a Non-Invasive Biomarker for Gastric Cancer
María José Maturana1, Oslando Padilla2, Pablo M Santoro1
1Department of Hematology and Oncology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Portugal 61, Santiago 8330023, Chile.
International Journal of Molecular Sciences
|April 17, 2025
Summary
This study introduces methylated Reprimo (RPRM) circulating cell-free DNA as a novel, non-invasive biomarker for detecting gastric cancer (GC) and monitoring treatment response. Elevated RPRM levels accurately identified GC and predicted treatment outcomes in patient cohorts.
Area of Science:
- Oncology
- Molecular Diagnostics
- Biomarker Discovery
Background:
- COVID-19 pandemic reversed declining gastric cancer (GC) diagnosis and mortality rates, emphasizing the need for cost-effective screening and treatment response evaluation.
- Circulating methylated cell-free DNA (cfDNA) of the tumor suppressor gene Reprimo (RPRM) is investigated as a potential non-invasive biomarker for GC.
Purpose of the Study:
- To evaluate the efficacy of methylated RPRM cfDNA as a non-invasive biomarker for gastric cancer detection.
- To assess the utility of methylated RPRM cfDNA in monitoring treatment response in GC patients.
- To determine the association of methylated RPRM cfDNA with premalignant conditions of the stomach.
Main Methods:
- Analysis of methylated RPRM cfDNA in three cohorts: GC patients vs. healthy donors (HDs), GC patients undergoing treatment, and a population-based screening cohort with various gastric conditions.
- Development of a fluorescence-based real-time PCR assay (MethyLight) for quantifying absolute methylated RPRM cfDNA copy numbers.
- Nested case-control substudy combining methylated RPRM cfDNA with pepsinogen (PG)-I/II ratio for enhanced detection.
Main Results:
- Cohort 1 showed significantly higher methylated RPRM cfDNA levels in GC patients (32,240.00 copies/mL) compared to HDs (139.00 copies/mL), with a trained model achieving 70.0% sensitivity and 80.2% specificity.
- In Cohort 2, responders demonstrated a significant decrease in RPRM levels post-treatment (p = 0.0042), indicating its role in monitoring treatment efficacy.
- Cohort 3 revealed a dose-dependent increase in positive methylation rates with disease progression, from 18.9% in normal participants to 71.2% in advanced GC. The combined RPRM and PG-I/II ratio showed 78.9% sensitivity for detecting high-grade dysplasia/early GC.
Conclusions:
- Methylated RPRM cfDNA serves as a direct non-invasive biomarker for gastric cancer detection.
- This biomarker is also predictive of treatment response in GC patients.
- The findings support the consideration of methylated RPRM cfDNA in GC screening and management strategies.
