Increased 5-hydroxymethylcytosine is a favorable prognostic factor of Helicobacter pylori-negative gastric cancer patients

BACKGROUND: Most gastric cancer (GC) patients are diagnosed at middle or late stage because the symptoms in early stage are obscure, which causes higher mortality rates of GC. Helicobacter pylori (H. pylori) was identified as a class I carcinogen and leads to aberrant DNA methylation/hydroxymethylation. 5-hydroxymethylcytosine (5-hmC) plays complex roles in gene regulation of tumorigenesis and can be considered as an activating epigenetic mark of hydroxymethylation. AIM: To explore the association between 5-hmC levels and the progression and prognosis of GC patients with or without H. pylori infection. METHODS: A retrospective cohort study was conducted to estimate the predicted value of 5-hmC level in the progression and prognosis of GC patients with different H. pylori infection status. A total of 144 GC patients were recruited. RESULTS: The levels of 5-hmC were significantly decreased in tumor tissues (0.076 ± 0.048) compared with the matched control tissues (0.110 ± 0.057, P = 0.001). A high level of 5-hmC was an independent significant favorable predictor of overall survival in GC patients (hazard ratio = 0.61, 95% confidence interval: 0.38-0.98, P = 0.040), the H. pylori-negative GC subgroup (hazard ratio = 0.30, 95% confidence interval: 0.13-0.68, P = 0.004) and the GC patients with TNM stage Ⅰ or Ⅱ (hazard ratio = 0.32, 95% confidence interval: 0.13-0.77, P = 0.011). CONCLUSION: Increased 5-hmC is a favorable prognostic factor in GC, especially for H. pylori-negative subgroups.