miR-129 as a Molecular Biomarker in Gastric Cancer and Its Association with Neurodegenerative and Vascular Pathology

MicroRNA-129 (miR-129) is a tumor suppressor involved in regulating oncogenic pathways, but its role in gastric adenocarcinoma and its potential connections to vascular and neurological dysfunction remain insufficiently defined.

To assess gastric juice-derived miR-129 as a diagnostic and prognostic biomarker for gastric cancer and to explore its associations with systemic inflammation, vascular impairment, and neurodegenerative changes.

A prospective study was conducted in 38 patients undergoing upper gastrointestinal endoscopy (22 with histologically confirmed gastric adenocarcinoma, 16 controls). Gastric juice was aspirated prior to biopsy, and miR-129-2-3p expression was quantified by means of RT-qPCR normalized to U6 RNA. Tumor stage, serum biomarkers (CEA, CA 19-9, LDH, and CRP), carotid index (Doppler ultrasound), and neuroimaging (MRI) were recorded. Statistical analyses included ANOVA, Mann-Whitney U, ROC curve analysis, and correlation testing.

miR-129 expression was significantly reduced in gastric cancer compared with controls (ANOVA: F(3,34) = 3.70, p = 0.021, η² = 0.25). ΔCt values increased progressively from controls to T2-T4 tumors, indicating stage-dependent downregulation. ROC analysis demonstrated moderate diagnostic performance (AUC = 0.75, 95% CI 0.54-0.92). Lower miR-129 levels correlated inversely with serum tumor markers (CEA, CA 19-9), LDH, and CRP. Patients with elevated carotid index (>1.3) and abnormal brain imaging findings exhibited significantly lower miR-129 expression (both p < 0.05).

Gastric juice-derived miR-129 is downregulated in gastric adenocarcinoma, with progressive decline across tumor stages. Its inverse association with systemic tumor and inflammatory markers, as well as vascular and neurological impairment, suggests that miR-129 may function as a minimally invasive, multi-system biomarker for integrated cancer and vascular-neurological risk assessment.