DNA Methylation of HOXA11 Gene as Prognostic Molecular Marker in Human Gastric Adenocarcinoma

Abstract

Hypermethylation of tumor suppressor genes and hypomethylation of oncogenes might be identified as possible biomarkers in gastric cancer (GC). We aimed to assess the DNA methylation status of selected genes in GC tissue samples and evaluate these genes’ prognostic importance on patient survival. Patients (99) diagnosed with GC and who underwent gastrectomy were included. We selected a group of genes (RAD51B, GFRA3, AKR7A3, HOXA11, TUSC3, FLI1, SEZ6L, GLDC, NDRG) which may be considered as potential tumor suppressor genes and oncogenes. Methylation of the HOXA11 gene promoter was significantly more frequent in GC tumor tissue (p = 0.006) than in healthy gastric mucosa. The probability of surviving longer (71.2 months (95% CI 57–85.3) vs. 44.3 months (95% CI 34.8–53.9)) was observed with unmethylated HOXA11 promoter in cancer tissues. Survival in patients with a methylation of HOXA11 promoter either in healthy gastric mucosa or gastric cancer tissue was twice as high as in patients with a methylation of HOXA11 promoter in both healthy gastric mucosa and cancer tissue (61.2 months (95% CI 50.9–71.4) vs. 28.5 months (95% CI 20.8–36.2)). Multivariate Cox analysis revealed the HOXA11 methylation as significantly associated with patients’ survival (HR = 2.4, 95% CI 1.19–4.86). Our results suggest that the HOXA11 gene might be a potential prognostic molecular marker in patients with gastric adenocarcinoma.

Keywords

• gastric adenocarcinoma
• methylation
• HOXA11
• survival