A panel of DNA methylated markers predicts metastasis of pN0M0 gastric carcinoma: a prospective cohort study

Dajun Deng,Xiaojing Cheng,Jing Zhou,Lianhai Zhang,Jiafu Ji,Zhaojun Liu

doi:10.1038/s41416-019-0552-0

Dajun Deng, Xiaojing Cheng + Show 4 more

Open Access

https://doi.org/10.1038/s41416-019-0552-0

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Abstract

BackgroundThe aim of this prospective study was to evaluate the feasibility of predicting GC metastasis using CDH1, GFRA1, P16 and ZNF382 DNA methylation as biomarkers.Methods198 GC patients without metastasis at the time of surgery resection were recruited into the double-blind cohort (NCT02159339). Gene methylation was analysed using MethyLight assays. GC metastasis and survival data were obtained from 178 patients with 94.7% compliance during follow-up.ResultsTwenty six cases of metastasis and 5 cases of recurrence were observed in 178 cases (17.4%) during the follow-up (median, 62.7 months). The GC metastasis rate for GFRA1 methylation-positive patients was significantly reduced compared with GFRA1 methylation-negative patients (odds ratio [OR]: 0.23, 95% confidence interval [CI] 0.08–0.66). Similar results were also observed using ZNF382 methylation as a predictor (OR: 0.17, 95% CI 0.06–0.47). A risk score including methylation of GFRA1 and ZNF382 was generated. The metastasis rate was significantly increased in high-risk GC patients (OR: 4.71, 95% CI: 1.85–12.00). GC patients with high risk had a shorter overall survival, especially for patients with stage I GC (P = 0.024).ConclusionsThe combination of GFRA1 and ZNF382 methylation is a biomarker panel for the prediction of GC metastasis.

Highlights

The aim of this prospective study was to evaluate the feasibility of predicting Gastric carcinoma (GC) metastasis using CDH1, GDNF family receptor a 1 (GFRA1), P16 and ZNF382 DNA methylation as biomarkers
We demonstrated that the GFRA1 and ZNF382 genes were methylated in human GC tissues and significantly associated with a low risk of GC metastasis in Chinese, Japanese, and Korean patients.[11]
The results showed that patients with ZNF382m-high GC had a significantly longer relapse-free survival (RFS) than those with ZNF382m-low GC in univariate analysis and multivariate analysis (Fig. 4a; Supplementary Table 6)

Summary

Introduction

The aim of this prospective study was to evaluate the feasibility of predicting GC metastasis using CDH1, GFRA1, P16 and ZNF382 DNA methylation as biomarkers. RESULTS: Twenty six cases of metastasis and 5 cases of recurrence were observed in 178 cases (17.4%) during the follow-up (median, 62.7 months). The metastasis rate was significantly increased in high-risk GC patients (OR: 4.71, 95% CI: 1.85–12.00). CONCLUSIONS: The combination of GFRA1 and ZNF382 methylation is a biomarker panel for the prediction of GC metastasis. Comprehensive studies have identified several genes associated with GC development and progression, a sensitive and specific biomarker capable of predicting prognosis and likelihood of metastasis is lacking.[6,7,8,9]

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Conclusion