Expression of Aquaporin-1, Aquaporin-3, and Aquaporin-5 Correlates with Nodal Metastasis in Colon Cancer

Abstract

Objectives: The clinical significance of aquaporin-1 (AQP1), aquaporin-3 (AQP3), and aquaporin-5 (AQP5) expression was analyzed in a large number of patients with colon cancer. Methods: AQP1, AQP3, and AQP5 expression was investigated based on the immunohistochemistry of tissue microarray specimens from 486 colon cancer patients who underwent curative surgery. Scores were given to the staining intensity and percentage of positive cells, and the staining score was defined as the sum of these scores then used to categorize the AQP expression as negative, weakly AQP-positive, or strongly AQP-positive. Results: A total of 298 (61.3%) patients were identified as strongly AQP1-positive (staining score ≥6), while 38 (7.8%) were strongly AQP3-positive and 145 (29.8%) were strongly AQP5-positive. The overexpression of AQP1, AQP3, and AQP5 was significantly correlated with lymph node metastasis in a multivariate logistic analysis (AQP1, p = 0.026; AQP3, p = 0.023; AQP5, p = 0.003). While the multivariate survival analysis, which included age, histology, TNM stage, and CEA level showed that the expression of AQP1, AQP3, and AQP5 had no effect on the overall survival and disease-free survival. Conclusions: The current study found a significant correlation between AQP1, AQP3, and AQP5 expression and lymph node metastasis in patients with surgically resected colon cancer.

Differential expression of aquaporin‐3 and aquaporin‐5 in pancreatic ductal adenocarcinoma

“…On the contrary, the highest AQP3 expression levels were found in poorly differentiated tumors that are usually more aggressive and later stages of the disease. Since tumorigenesis of PDA occurs in ductal epithelial cells and in moderately differentiated tumors a positive correlation was found between AQP5 and Ki‐67, one of the most important markers of active cellular proliferation, this indicates that AQP5 may play an important role in PDA progression and proliferation, as reported for other types of cancer and depicted in our proposed model (Fig. ).…”

“…Recently, an increasing number of reports showed that AQP3 and AQP5 are abundantly expressed in different tumors such as squamous cell carcinoma of the skin, colon cancer, breast cancer, lung cancer, ovarian cancer, cervical cancer, and prostate cancer, playing key roles in cell proliferation and migration . In tumors, cells divide more frequently, thus needing more energy to maintain their rapid growth.…”

Aquaporin-3 mediates hydrogen peroxide-dependent responses to environmental stress in colonic epithelia

“…Although AQP3 has not been identified as a monogenic cause of IBD, patients with ulcerative colitis have significantly lower expression of epithelial AQP3 during both inflammation and clinical remission (17). Conversely, AQP3 expression is highly increased in many colon carcinomas and is correlated with metastatic spread (37). As shown here, AQP3-dependent H 2 O 2 cellular entry increases colonic epithelial migration, and it is plausible that AQP3-facilliated H 2 O 2 transport may play a role in the development of colonic cancers and metastases.…”

Role of Aquaporin 1 Signalling in Cancer Development and Progression

“…In the case of colon cancer, Moon and colleagues showed expression of AQP1 in colonic adenoma, primary and secondary colon cancer, but not in normal colonic mucosa, suggesting a role of AQP1 in the early stage of colon cancer tumorigenesis [19]. Additionally, its expression was reported to be associated with clinical characteristics known to be prognostic such as histological grade and status of lympho-vascular invasion and nodal involvement [18,22,23,27,28,29,30]. These findings suggested the link between AQP1 and cancer biological functions, which act to drive cancer development and progression.…”