Impact of Helicobacter pylori Infection Status on SEPTIN9 and SDC2 Methylation Levels and Their Association with Clinical Outcomes in Elderly Patients with Gastric Mucosal Intestinal Metaplasia

Background/Aims: The impact of dynamic Helicobacter pylori (Hp) infection status on DNA methylation and progression risk in elderly patients with gastric intestinal metaplasia (IM) remains unclear. This study evaluated the associations of Hp infection status with SEPTIN9 and SDC2 methylation levels and whether baseline methylation markers were associated with subsequent clinical outcomes.

Materials and Methods: This single-center retrospective cohort study enrolled 200 older adults with IM. Hp infection status was dynamically defined over follow-up as persistent infection, successful eradication, or sustained negative infection. Baseline SEPTIN9 and SDC2 methylation levels were quantified in formalin-fixed, paraffin-embedded tissue samples using quantitative methylation-specific polymerase chain reaction (qMSP). Kaplan–Meier analysis and Cox proportional hazards regression were used to evaluate progression risk. Predictive performance was assessed using Harrell’s C-index and time-dependent receiver operating characteristic analysis. Because methylation was measured only at baseline, the analyses were designed to evaluate baseline methylation markers rather than dynamic methylation changes over time.

Results: During a median follow-up of 3.86 years, 38 patients (19.0%) experienced disease progression. Persistent Hp infection was associated with higher SEPTIN9 and SDC2 methylation levels (P < .01). Combined double-positive methylation status was associated with an increased risk of IM progression (adjusted hazard ratio [HR] = 3.12, 95% CI: 1.53 6.38, P = .002), with the strongest association observed among patients with persistent Hp infection. Incorporation of the combined methylation indicator improved model discrimination (C-index 0.75 vs. 0.68) and the 5-year area under the curve (0.77 vs. 0.69).

Conclusion: Baseline SEPTIN9 and SDC2 methylation levels differed according to the Hp infection status, with the highest levels observed among patients with persistent Hp infection. Baseline combined methylation status was associated with an increased risk of IM progression and may provide incremental value for risk stratification. These findings should be interpreted as baseline associations.

Cite this article as: Yu Z, Ni H, Chen X, Xiao K. Impact of Helicobacter pylori infection status on SEPTIN9 and SDC2 methylation levels and their association with clinical outcomes in elderly patients with gastric mucosal intestinal metaplasia. Turk J Gastroenterol. Published online July 21, 2026. doi: 10.5152/tjg.2026.26162.