Circulating PANX1, P2RY2, and TLR3 Profiles in Gastric Cancer: A Preliminary Molecular Study

Gastric cancer is strongly associated with chronic inflammation and dysregulated immune signaling. Molecules involved in purinergic and innate immune pathways, including Toll-like receptor 3 (TLR3), P2Y purinoceptor 2 (P2RY2), and pannexin-1 (PANX1), may contribute to gastric cancer biology; however, their combined clinical relevance remains unknown. This study included 45 patients with gastric cancer and 45 healthy controls. The gene expression levels of TLR3, P2RY2, and PANX1 were analyzed using RT-PCR, and serum protein concentrations were measured using ELISA. Group comparisons, logistic regression, and ROC analyses were performed to evaluate the diagnostic performance. TCGA-STAD-based immune infiltration analyses were conducted using the TIMER platform, and prognostic significance was assessed using Kaplan-Meier survival analysis. Although alterations in gene expression were observed, none reached statistical significance. At the protein level, PANX1 was significantly elevated in patients with gastric cancer and was independently associated with disease status, whereas TLR3 and P2RY2 showed no significant circulating alterations. TIMER analysis demonstrated positive correlations between TLR3 and PANX1 expression and several immune cell populations, whereas P2RY2 expression showed predominantly negative correlations with immune cell infiltration. Kaplan-Meier analysis revealed that high PANX1 and TLR3 expression levels were associated with improved overall survival. ROC analyses indicated limited diagnostic accuracy for each marker. Collectively, our experimental findings provide evidence only for elevated circulating PANX1 in patients with gastric cancer. In contrast, the observations regarding TLR3 and P2RY2 were not statistically significant in our cohort and should therefore be considered exploratory and hypothesis-generating. Complementary bioinformatic analyses suggest that these molecules may participate in immune-related signaling pathways in gastric cancer; however, these observations require validation in independent tissue-based and larger prospective studies.