Huang W.-J.YUNG-MING JENGHONG-SHIEE LAIFong I.-U.Sheu F.-Y.B.Lai P.-L.RAY-HWANG YUAN2020-03-062020-03-0620151932-6203https://www.scopus.com/inward/record.uri?eid=2-s2.0-84928911836&doi=10.1371%2fjournal.pone.0119181&partnerID=40&md5=7159f88260e9405d147e19c29d81738chttps://scholars.lib.ntu.edu.tw/handle/123456789/473315Carbonic anhydrase IX (CA-IX), a hypoxia marker, correlates with tumor progression in a variety of human cancers. However, the role of CA-IX in hepatocellular carcinomas (HCCs) remains largely unknown.We examined the expression of 277 unifocal, resectable, primary HCC tumors using immunohistochemistry. The CA-IX protein was expressed in 110 of the 227 (48.5%) HCC tumors. The expression of CA-IX correlated with younger age (P = 0.0446), female sex (P = 0.0049), high serum α-fetoprotein levels (P<1×10-6), larger tumor size (P = 0.0031), high tumor grade P<1×10-6) and high tumor stage (P = 1.5x10-6). Patients with HCC tumors that expressed CA-IX were more likely to have lower 5-year diseasefree survival (DFS; P = 0.0001) and 5-year overall survival (OS; P<1×10-6). The multivariate analysis indicated that CA-IX expression was an independent predictor for high tumor stage (P = 0.0047) and DFS (P = 0.0456), and a borderline predictor for OS (P = 0.0762). Furthermore, CA-IX expression predicted poor DFS and OS in patients with high tumor stage (P = 0.0004 and P<1×10-6, respectively). Interestingly, CA-IX expression might contribute to the worse prognosis of female patients with advanced HCCs. Our study indicates the expression of the CA-IX protein is a crucial predictor of poor prognosis in resectable HCC, and it is also an unfavorable prognostic predictor in HCC patients with high tumor stage. ? 2015 Huang et al.[SDGs]SDG3alpha fetoprotein; carbonate dehydratase IX; CA9 protein, human; carbonate dehydratase; carbonate dehydratase IX; tumor antigen; tumor marker; adolescent; adult; age; aged; Article; cancer prognosis; cancer staging; controlled study; correlation analysis; disease free survival; female; gender; human; immunohistochemistry; liver cell carcinoma; major clinical study; male; multivariate analysis; overall survival; protein expression; tumor volume; Carcinoma, Hepatocellular; cell hypoxia; cytology; disease course; gene expression regulation; liver; Liver Neoplasms; metabolism; middle aged; pathology; prognosis; recurrent disease; tumor invasion; very elderly; young adult; Adolescent; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carbonic Anhydrase IX; Carbonic Anhydrases; Carcinoma, Hepatocellular; Cell Hypoxia; Disease Progression; Female; Gene Expression Regulation, Neoplastic; Humans; Liver; Liver Neoplasms; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Prognosis; Recurrence; Young Adultjournal article10.1371/journal.pone.0119181257389582-s2.0-84928911836