Prognostic Assessment of Aquaporins in Pancreatic Adenocarcinoma: An In Silico Analysis

Background: Pancreatic cancer is the sixth leading cause of death with a limited validated biomarker. Finding and validating diagnostic/prognostic markers can be improved by combining both forms of data in a multi-omics approach, which can offer a more comprehensive outcome. Methods: GEO datasets were utilized to identify differentially expressed aquaporins in pancreatic cancer and validated through TCGA-PAAD data. Protein Data Commons (PDC) was used to analyse differentially expressed proteins in PAAD. Functional enrichment analysis and immune cell infiltration analysis were conducted through SRplot and TIMER database, respectively. Survival association was studied using Cox proportional regression and Kaplan-Meier analysis. Results: A significant downregulation of AQP1, AQP8, AQP11, AQP12A and AQP12B expression and upregulation of AQP5, AQP6 and AQP9 expression were observed in PAAD (p-value = 0.0001). This analysis revealed that overexpression of AQP6 was significantly associated with the poor outcome of the PAAD patients (HR=1.8399, p=0.037). Additionally, we found that alcohol history and low expression of AQP1 and AQP9 were associated with low survival among the PAAD patients and these aquaporins were strongly correlated with immune infiltrates. Discussion: Our research underscores the important role of aquaporins, especially AQP6, in pancreatic adenocarcinoma prognosis. The correlation of AQP1 and AQP9 with immune cell infiltration and patient survival indicates their promise as immuno-oncological markers. These results validate the use of aquaporins as diagnostic and prognostic targets in PAAD treatment. Conclusion: Our results suggested that AQP6 might be a novel prognostic marker in PAAD patients. Additionally, AQP12A and AQP12B may act as distinctive diagnostic markers to detect pancreatic adenocarcinoma.