Prognostic Value of Combined Aquaporin 3 and Aquaporin 5 Overexpression in Hepatocellular Carcinoma

Abstract

Background. Aquaporin (AQP) 3 and AQP 5 are involved in tumorigenesis and tumor progression of several tumor types. Aim. To investigate expression patterns and clinical significance of AQP3 and AQP5 in hepatocellular carcinoma (HCC). Methods. Immunohistochemistry was performed to detect the expression of AQP3 and AQP5 in HCC tissues. Results. Immunohistochemistry analysis showed the increased expression of AQP3 and AQP5 protein levels in HCC tissues compared with their adjacent nonneoplastic tissues (both P < 0.001). In addition, combined AQP3 and AQP5 protein expression was significantly associated with serum AFP (P = 0.008), tumor stage (P = 0.006), and tumor grade (P = 0.006). Moreover, HCC patients highly expressing both AQP3 and AQP5 proteins had worse 5-year disease-free survival and 5-year overall survival (P = 0.002 and 0.005, resp.). Furthermore, the Cox proportional hazards model showed that combined AQP3 and AQP5 protein expression was an independent poor prognostic factor for both 5-year disease-free survival (P = 0.009) and 5-year overall survival (P = 0.01) in HCC. Conclusion. Our data suggest for the first time that the aberrant expression of AQP3 and AQP5 proteins may be strongly related to tumor progression and prognosis in patients with HCC. The overexpression of AQP3 in combination with upregulation of AQP5 may be an unfavorable prognostic factor for HCC.

Aquaporin-3 Controls Breast Cancer Cell Migration by Regulating Hydrogen Peroxide Transport and Its Downstream Cell Signaling

“…Increasing evidence shows that a correlation exists between AQP3 expression and cancer progression and prognosis, particularly in distant or lymphatic metastasis of colorectal, esophageal, hepatocellular, and gastric malignant cancers (11)(12)(13)(14). In the current study, we showed that overexpressing AQP3 promoted the migration of breast cancer cells toward CXCL12 in association with higher intracellular H 2 O 2 levels and enhanced susceptibility to Akt activation in vitro.…”

“…AQP3 is expressed in various cancer cells derived from diverse types of cancer tissues, including breast, colon, and lung (9, 10). Recent results from clinical studies have suggested the relevance of AQP3 expression in tumor progression and the prognosis of several malignant cancers (11)(12)(13)(14). In vitro studies using cancer cell lines have implicated AQP3 expression in cancer cell proliferation and migration (15-17).…”

Urine AQP5 is a potential novel biomarker of diabetic nephropathy

“…A selective defect in lacrimal gland AQP5 trafficking is responsible for Sjögren’s syndrome characterized by dry eye and mouth (Tsubota, Hirai, King, Agre, & Ishida, 2001). Elevated AQP5 expression is associated with advanced tumor stage, positive distant metastasis, and/or unfavorable prognosis in several types of cancer (Guo et al, 2013; Watanabe et al, 2009; Yang, Shi, Cheng, & Deng, 2006; Zhang et al, 2010). However, pathological expression of AQP5 in kidney had not been described until our recent report (Wu et al, 2013).…”

Expression of AQP1 Was Associated with Apoptosis and Survival of Patients in Gastric Adenocarcinoma

“…AQPs are strongly expressed by various tumor cells, especially those from aggressive tumors [2][3][4] . The involvement of AQPs in cell migration and proliferation suggests that AQPs could play key roles in tumor biology [5][6][7] . Consistently, AQP1-expressing tumor cells demonstrate enhanced metastatic potential and increased local infiltration [5,8,9] .…”