Cancer Res Treat.  2022 Oct;54(4):1157-1166. 10.4143/crt.2021.997.

Aberrant DNA Methylation Maker for Predicting Metachronous Recurrence After Endoscopic Resection of Gastric Neoplasms

• Shin CM
• Kim N
• Yoon H
• Choi YJ
• Park JH
• Park YS
• Lee DH

• KMID: 2534195
• DOI: http://doi.org/10.4143/crt.2021.997

Abstract

Purpose
This study aimed to investigate whether MOS methylation can be useful for the prediction of metachronous recurrence after endoscopic resection of gastric neoplasms.
Materials and Methods
From 2012 to 2017, 294 patients were prospectively enrolled after endoscopic resection of gastric dysplasia (n=171) or early gastric cancer (n=123). When Helicobacter pylori was positive, eradication therapy was performed. Among them, 124 patients completed the study protocol (follow-up duration > 3 years or development of metachronous recurrence during the follow-up). Methylation levels of MOS were measured at baseline using quantitative MethyLight assay from the antrum.
Results
Median follow-up duration was 49.9 months. MOS methylation levels at baseline were not different by age, sex, and current H. pylorii infection, but they showed a weak correlation with operative link on gastritis assessment (OLGA) or operative link on gastric intestinal metaplasia assessment (OLGIM) stages (Spearman’s ρ=0.240 and 0.174, respectively; p < 0.05). During the follow-up, a total of 20 metachronous gastric neoplasms (13 adenomas and 7 adenocarcinomas) were developed. Either OLGA or OLGIM stage was not useful in predicting the risk for metachronous recurrence. In contrast, MOS methylation high group (≥ 34.82%) had a significantly increased risk for metachronous recurrence compared to MOS methylation low group (adjusted hazard ratio, 4.76; 95% confidence interval, 1.54 to 14.79; p=0.007).
Conclusion
MOS methylation can be a promising marker for predicting metachronous recurrence after endoscopic resection of gastric neoplasms. To confirm the usefulness of MOS methylation, validation studies are warranted in the future (ClinicalTrials No. NCT04830618).

Keyword

Methylation; Stomach neoplasms; Second primary neoplasms; Recurrence

Figure

• 

  Fig. 1 Receiver operating characteristic curve analysis to determine a cutoff value of MOS methylation level to predict the risk for metachronous recurrence (n=124). Optimal cutoff value was 35.82% and sensitivity, specificity, PPV and NPV were 80.0%, 53.2%, 26.7%, and 92.6%, respectively. AUC, area under curve; NPV, negative predictive value; PPV, positive predictive value.

• 

  Fig. 2 MOS methylation levels according to age (A), family history of gastric cancer (B), synchronous gastric lesions (C), current Helicobacter pylori infection (D), and OLGA (E) and OLGIM (F) stages (n=261). OLGA, operative link on gastritis assessment; OLGIM, operative link on gastric intestinal metaplasia assessment.

• 

  Fig. 3 Kaplan-Meier curves for cumulative incidences of metachronous recurrence according to atrophic gastritis (A), OLGA stage (B), intestinal metaplasia (C), OLGIM stage (D), MOS methylation status (E, F, n=124). Atrophic gastritis and intestinal metaplasia were defined as the presence of histologic atrophy (score 1–3) and intestinal metaplasia (score 1–3), respectively, at either antrum or corpus by the updated Sydney scoring system. The cutoff value (35.82%) of high or low level of MOS methylation was determined by receiver operating characteristic curve analysis. OLGA, operative link on gastritis assessment; OLGIM, operative link on gastric intestinal metaplasia assessment.

Reference

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