A panel of DNA methylated markers predicts metastasis of pN0M0 gastric carcinoma: a prospective cohort study
Menée sur 198 patients atteints d'un carcinome gastrique de stade pN0M0 (durée médiane de suivi : 62,7 mois), cette étude met en évidence l'intérêt de déterminer le statut de méthylation des gènes GFRA1 et ZNF382 pour prédire le risque de métastases
Background : 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.
Methods : 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.
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 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).
Conclusions : The combination of GFRA1 and ZNF382 methylation is a biomarker panel for the prediction of GC metastasis.
British Journal of Cancer , résumé, 2019