Expression of aquaporin 1, 3 and 5 in colorectal carcinoma: correlation with clinicopathological characteristics and prognosis

Abstract

Background: Prognostic biomarkers in colorectal carcinoma (CRC) have an important role in therapeutic strategy. Studies have shown that high expression of Aquaporin (AQP) is associated with poor prognosis in a variety of human tumors. AQP is involved in the initiation and development of CRC. The present study aimed to investigate the correlation between the expression of AQP1, 3 and 5 and clinicopathological features or prognosis in CRC. Methods: The AQP1, 3 and 5 expressions were analyzed based on the immunohistochemical staining of tissue microarray specimens including 112 patients with CRC between June 2006 and November 2008. The expression score of AQP (Allred_score and H_score) was digitally obtained with Qupath software. Patients were divided into high or low expression subgroups based on the optimal cut-off values. The relationship between expression of AQP and clinicopathological characteristics were evaluated using chi-square test, t-test, or one-way ANOVA, when appropriate. Survival analysis of 5-year progression free survival (PFS) and overall survival (OS) was performed with time-dependent ROC, Kaplan-Meier curves, univariate and multivariate COX analysis. Results: The AQP1, 3 and 5 expressions were associated with regional lymph node metastasis, histological grading, and tumor location in CRC, respectively (p < 0.05). Kaplan-Meier curves showed that patients with high AQP1 expression had worse 5-year PFS than those with low AQP1 expression (Allred_score: 47% vs. 72%, p = 0.015; H_score: 52% vs. 78% p = 0.006), as well as 5-year OS (Allred_score: 51% vs. 75%, p = 0.005; H_score: 56% vs. 80%, p = 0.002). Multivariate Cox regression analysis indicated that AQP1 expression was an independent risk prognostic factor (p = 0.033, HR = 2.274, HR95% CI: 1.069–4.836). There was no significant correlation between the expression of AQP3 and 5 and the prognosis. Conclusion: The AQP1, 3 and 5 expressions correlate with different clinicopathological characteristics and the AQP1 expression may be a potential biomarker of prognosis in CRC.