title: Prognostic significance of aquaporins in human biliary tract carcinoma.
abstract: Aquaporins (AQPs) are important in controlling bile formation, however, the exact role of AQPs in human biliary tract carcinogenesis has not been clearly defined. In this study, we analyzed AQP-1, -4, -5 and -8 expression immunohistochemically using tissue microarrays (TMAs) in 81 samples. (45 gallbladder carcinomas and 36 bile duct carcinomas). The survival of patients with high AQP-5 expression was longer compared to that of patients with low AQP-5 expression (P=0.017). Cox's proportional hazard model revealed that AQP-5 expression was an independent prognostic factor (RR, 0.38; P=0.025). Chi-square analysis revealed that high AQP-5 expression correlated to small tumor size in biliary tract carcinoma patients (P=0.006). With regard to the expression of other AQPs, depth of tumor invasion, histological type and serum carbohydrate antigen 19-9 (CA19-9) were associated with high AQP-1 expression (P=0.039, 0.011 and 0.032). However, AQP-4 and AQP-8 expression had no association with clinicopathological factors. Among the 10 patients who underwent gemcitabine (GEM) plus S-1 postoperative chemotherapy, the group of patients (n=5) with high AQP-5 expression were associated with higher rates of both overall and disease-free survival (log-rank P=0.033, 0.002). In conclusion, the results of this study suggest that AQP-5 expression may be associated with prognosis and drug sensitivity in biliary tract carcinoma.
authors.affiliation: Department of Surgery and Science, University of Toyama, Toyama, Toyama 930-0194, Japan. sekky@med.u-toyama.ac.jp
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sekine
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Shimada
authors.forename: Takuya
authors.initials: T
authors.lastname: Nagata
authors.forename: Makoto
authors.initials: M
authors.lastname: Moriyama
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Omura
authors.forename: Tomoko
authors.initials: T
authors.lastname: Watanabe
authors.forename: Ryouta
authors.initials: R
authors.lastname: Hori
authors.forename: Isaku
authors.initials: I
authors.lastname: Yoshioka
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Okumura
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Sawada
authors.forename: Junya
authors.initials: J
authors.lastname: Fukuoka
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsukada
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D051398:Aquaporin 1 / Q000378:metabolism; D051401:Aquaporin 4 / Q000378:metabolism; D051402:Aquaporin 5 / Q000378:metabolism*; D020346:Aquaporins / Q000378:metabolism*; D001650:Bile Duct Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality* / Q000601:surgery; D014408:Biomarkers, Tumor / Q000378:metabolism; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D004338:Drug Combinations; D005260:Female; D005706:Gallbladder Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality* / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000627:therapeutic use; D011379:Prognosis; D005641:Tegafur / Q000627:therapeutic use; D000093542:Gemcitabine
chemical_list: C496020:AQP1 protein, human; C496030:AQP4 protein, human; C496036:AQP5 protein, human; D051401:Aquaporin 4; D051402:Aquaporin 5; D020346:Aquaporins; D014408:Biomarkers, Tumor; D004338:Drug Combinations; C108330:aquaporin 8; D003841:Deoxycytidine; D051398:Aquaporin 1; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000093542:Gemcitabine