Vitamin D-regulated miRNA expression in tumoral and normal adjacent tissue of localized gastric cancer patients: the impact on survival and time to relapse.

Abstract

Background: Gastric cancer (GC) is driven by genetic, epigenetic, and environmental factors, with dysregulated microRNAs (miRNAs) influencing key biological processes and vitamin D signaling through vitamin D receptor modulation, impacting tumor prognosis. The aim of this study is to correlate the expression of vitamin D-related miRNAs in tumor tissue and normal adjacent tissue (NAT) in GC with patient survival.

Methods: The study involved 77 patients with localized GC, with time to relapse (TTR) and overall survival (OS) as primary and secondary endpoints, respectively. The study investigated miRNA expression levels in NAT and tumor and their association with patient characteristics.

Results: The analysis revealed that miR-106b, miR-181b-5p, miR-181a-5p and miR-181d-5p were upregulated in tumor tissue, whereas miR-143 and miR-145 were downregulated. Patients with vitamin D deficiency (levels <30 ng/mL) showed downregulation of miR-145 in the NAT (P=0.02). The study found that downregulation of miR-181b-5p, miR-106b, and miR-181c-5p in NAT correlated with higher relapse risk (P=0.02, P=0.003, P=0.03). Furthermore, lower OS rates were significantly linked to the downregulation of miR-106b and miR-99b-3p in NAT (P<0.001, P=0.004). These findings indicate that specific miRNA downregulation in NAT is associated with poorer prognosis and increased relapse likelihood in GC patients. Additionally, miRNA expression patterns in NAT may indicate a predisposition to tumor recurrence.

Conclusions: The study concludes that miRNA dysregulation in non-neoplastic gastric mucosa suggests these tissues may be cancer-prone environments.