Abstract
Carbonic 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<1x10-6), larger tumor size (P = 0.0031), high tumor grade P<1x10-6) and high tumor stage (P = 1.5x10-6). Patients with HCC tumors that expressed CA-IX were more likely to have lower 5-year disease-free survival (DFS; P = 0.0001) and 5-year overall survival (OS; P<1x10-6). 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<1x10-6, 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.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, in Taiwan, southern China, Southeast Asia, and sub-Saharan Africa, and the incidence of HCC is PLOS ONE | DOI:10.1371/journal.pone.0119181 March 4, 2015carbonic anhydrase IX (CA-IX) Expression in Resectable HCC increasing in Western countries [1]
The identification of molecular markers that correlate with tumor progression and poor prognosis is crucial to establishing effective treatment plans for HCC patients
A total of 227 unifocal, primary HCC tumors surgically resected from patients at National Taiwan University Hospital (NTUH) from July 1988 to September 1996 were used on this study retrospectively
Summary
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, in Taiwan, southern China, Southeast Asia, and sub-Saharan Africa, and the incidence of HCC is PLOS ONE | DOI:10.1371/journal.pone.0119181 March 4, 2015CA-IX Expression in Resectable HCC increasing in Western countries [1]. The major risk factors for HCC are hepatitis B and C, liver cirrhosis, and exposure to environmental carcinogens such as aflatoxin [2]. Surgical resection and various methods of tumor ablation methods can be curative or prolong survival, the outcome for HCC patients remains poor. This is true in patients with advancedstage HCC because the tumor has often spread throughout the liver via the intrahepatic portal venous system, and a considerable number of HCC patients develop postoperative tumor recurrence [3]. The identification of molecular markers that correlate with tumor progression and poor prognosis is crucial to establishing effective treatment plans for HCC patients
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