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DOI: 10.1055/s-0038-1668956
Circulating hypoxia marker carbonic anhydrase IX (CA9) in patients with hepatocellular carcinoma and patients with cirrhosis
Publikationsverlauf
Publikationsdatum:
13. August 2018 (online)
Background and aims:
Expression of carbonic anhydrase IX (CA9), an enzyme expressed in response to hypoxia, acidosis and oncogenic alterations, is reported to be a prognostic factor in HCC patients. Here we evaluated CA9 levels in HCC and cirrhosis patients.
Methods:
HCC and cirrhosis patients were prospectively recruited and serum CA9 levels were determined. A healthy cohort for comparison was included. CA9 levels were compared to stages of cirrhosis and HCC stages. The association of the CA9 levels and overall survival (OS) was assessed. Furthermore, immunohistochemical CA9 expression in HCC and cirrhosis was evaluated.
Results:
215 patients with HCC were included. The median serum CA9 concentration in patients with HCC was 370 pg/ml and significantly higher than in a healthy cohort. Patients with advanced cancer stages (BCLC and ALBI score) had significant higher levels of CA9 in the serum. HCC patients with high serum CA9 concentrations (> 400 pg/ml) had an increased mortality risk (hazard ratio (HR) 1.690, 95% confidence interval (CI) 1.017 – 2.809, P= 0.043). Serum CA9 concentration in cirrhotic patients did not differ significantly from HCC patients. Higher CA9 levels in cirrhotic patients (n = 65) correlated significantly with portal hypertension and esophageal varices. Patients with ethanol induced cirrhosis had the highest CA9 levels in both cohorts. Levels of CA9 did not correlate with immunohistochemical expression in HCC patients. CA9 is highly expressed in ductular reactions, irregular bile ducts, a phenomenon occurring in damaged livers.
Conclusions:
We conclude that a high CA9 level is a possible prognostic indicator for a poor outcome in HCC patients. The high CA9 levels are probably associated with portal hypertension in cirrhosis patients. The source of serum CA9, especially in cirrhosis, remains unclear and needs further investigation, especially because of the missing correlation of positive IHC and serum CA9 levels. Ductular reactions in liver cirrhosis may be a source.
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