Rationale and Objective: Recently, interest in the role of aquaporin 1 (AQP1) in human gastrointestinal carcinogenesis has developed. However, to date no studies have examined relationships between AQP1 expression and specific characteristics of gastric adenocarcinoma. Methods: We investigated 109 specimens of primary gastric adenocarcinoma and their corresponding normal gastric mucosa using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) to determine AQP1 expression. We then evaluated disease free survival (DFS) and overall survival (OS) in these patients in association with AQP1 expression. Results: Both immunohistochemical and RT-PCR analyses identified increased AQP1 expression in tumors from patients with gastric adenocarcinoma (p < 0.001). The 3-year DFS and OS rates were higher in the AQP1-negative group than in the positive group (DFS: 77.2 vs. 52.8%, p < 0.001; OS: 85.1 vs. 70.7%, p < 0.001). The 5-year DFS and OS rates exhibited a similar trend (p < 0.001). Subgroup analysis of patients with early gastric adenocarcinoma (stages I and II) revealed a total 5-year OS of 90.0%, with 5-year OS being higher in the AQP1-negative group than in the positive group (95.2 vs. 84.2%). Furthermore, incidence of tumor recurrence following surgical treatment was significantly higher in the AQP1-positive group (4/19, 21.1%) compared with the negative group (0/21, 0%). Conclusions: Our study demonstrates that AQP1 plays an important role in gastric adenocarcinoma and may therefore represent a novel therapeutic target and prognostic marker in this disease.

1.
Gao LJ, Gu PQ, Zhao W, Ding WY, Zhao XQ, et al: The role of globular heads of the C1q receptor in HPV 16 E2-induced human cervical squamous carcinoma cell apoptosis is associated with p38 MAPK/JNK activation. J Transl Med 2013;11:118.
2.
Sreedharan S, Petros JA, Master VA, Ogan K, Pattaras JG, et al: Aquaporin-1 protein levels elevated in fresh urine of renal cell carcinoma patients: potential use for screening and classification of incidental renal lesions. Dis Markers 2014;2014:135649.
3.
Kusayama M, Wada K, Nagata M, Ishimoto S, Takahashi H, et al: Critical role of aquaporin 3 on growth of human esophageal and oral squamous cell carcinoma. Cancer Sci 2011;102:1128-1136.
4.
Shimizu H, Shiozaki A, Ichikawa D, Fujiwara H, Konishi H, et al: The expression and role of Aquaporin 5 in esophageal squamous cell carcinoma. J Gastroenterol 2014;49:655-666.
5.
Clapp C, Martínez de la Escalera G: Aquaporin-1: a novel promoter of tumor angiogenesis. Trends Endocrinol Metab 2006;17:1-2.
6.
Nico B, Ribatti D: Aquaporins in tumor growth and angiogenesis. Cancer Lett 2010;294:135-138.
7.
Guo X, Sun T, Yang M, Li Z, Li Z, et al: Prognostic value of combined aquaporin 3 and aquaporin 5 overexpression in hepatocellular carcinoma. Biomed Res Int 2013;2013:206525.
8.
Jiang Y: Aquaporin-1 activity of plasma membrane affects HT20 colon cancer cell migration. IUBMB Life 2009;61:1001-1009.
9.
El Hindy N, Bankfalvi A, Herring A, Adamzik M, Lambertz N, et al: Correlation of aquaporin-1 water channel protein expression with tumor angiogenesis in human astrocytoma. Anticancer Res 2013;33:609-613.
10.
Hara-Chikuma M, Verkman AS: Aquaporin-3 facilitates epidermal cell migration and proliferation during wound healing. J Mol Med (Berl) 2008;86:221-231.
11.
Skowronska A, Mlotkowska P, Eliszewski M, Nielsen S, Skowronski MT: Expression of aquaporin 1, 5 and 9 in the ovarian follicles of cycling and early pregnant pigs. Physiol Res 2015;64:237-245.
12.
Shen L, Zhu Z, Huang Y, Shu Y, Sun M, et al: Expression profile of multiple aquaporins in human gastric carcinoma and its clinical significance. Biomed Pharmacother 2010;64:313-318.
13.
Aishima S, Kuroda Y, Nishihara Y, Taguchi K, Iguchi T, et al: Down-regulation of aquaporin-1 in intrahepatic cholangiocarcinoma is related to tumor progression and mucin expression. Hum Pathol 2007;38:1819-1825.
14.
De Luca A, Vassalotti G, Pelagalli A, Pero ME, Squillacioti C, et al: Expression and localization of aquaporin-1 along the intestine of colostrum suckling buffalo calves. Anat Histol Embryol 2015;44:391-400.
15.
Kwon SJ: Evaluation of the 7th UICC TNM staging system of gastric cancer. J Gastric Cancer 2011;11:78-85.
16.
King LS, Agre P: Pathophysiology of the aquaporin water channels. Annu Rev Physiol 1996;58:619-648.
17.
Wei M, Shi R, Zeng J, Wang N, Zhou J, et al: The over-expression of aquaporin-1 alters erythroid gene expression in human erythroleukemia K562 cells. Tumour Biol 2015;36:291-302.
18.
Tan M, Shao C, Bishop JA, Feng Z, Trock BJ, et al: Aquaporin-1 promoter hypermethylation is associated with improved prognosis in salivary gland adenoid cystic carcinoma. Otolaryngol Head Neck Surg 2014;150:801-807.
19.
Chen R, Shi Y, Amiduo R, Tuokan T, Suzuk L: Expression and prognostic value of aquaporin 1, 3 in cervical carcinoma in women of Uygur ethnicity from Xinjiang, China. PLoS One 2014;9:e98576.
20.
Esteva-Font C, Jin BJ, Verkman AS: Aquaporin-1 gene deletion reduces breast tumor growth and lung metastasis in tumor-producing MMTV-PyVT mice. FASEB J 2014;28:1446-1453.
21.
Wu Z, Li S, Liu J, Shi Y, Wang J, et al: RNAi-mediated silencing of AQP1 expression inhibited the proliferation, invasion and tumorigenesis of osteosarcoma cells. Cancer Biol Ther 2015;16:1332-1340.
22.
Sun WJ, Lu MD, Yu YJ, Wang FH, Jiang SS, et al: Protein and mRNA expression of aquaporin-1 in gastric tumors and its clinic significance. Chin J General Surg 2010;25:414-415.
23.
Shum H, Rajdev L: Multimodality management of resectable gastric cancer: a review. World J Gastrointest Oncol 2014;6:393-402.
24.
Cho JY: Molecular diagnosis for personalized target therapy in gastric cancer. J Gastric Cancer 2013;13:129-135.
25.
Yun P, Zhao XY, Xu M, Fang H, Wang Q, et al: Decreased core-fucosylation contributes to malignancy in gastric cancer. PLoS One 2014;9:e94536.
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