Clinical Study

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



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.


198 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.


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 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).


The combination of GFRA1 and ZNF382 methylation is a biomarker panel for the prediction of GC metastasis.

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Author information

D.D. and J.J. were responsible for conception and design of the study. J.Z., Z.L. and X.C. performed experiments. Z.L. and X.C. contributed to the design and the final interpretation of statistical analysis. X.C, L.Z., J.J. and Z.L. contributed to the patient sample and data collection. Z.L., X.C. and D.D. wrote the manuscript.

Correspondence to Dajun Deng or Jiafu Ji.

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The authors declare no competing interests.

Ethics approval and consent to participate

The Institution Review Board of Peking University Cancer Hospital & Institute approved this study and was carried out in accordance with the principles outlined in the Declaration of Helsinki. Informed consent was obtained from each patient prior to their inclusion in the study.


This work is supported by grants from the National Natural Science Foundation of China (no. 81402031), the Beijing Municipal and Technology Commission (Z151100001615022), the Science Foundation of Peking University Cancer Hospital (2017–25) and the Beijing Municipal Commission of Health and Family Planning (PXM2018_026279_000005).

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