Circulating hypoxia marker carbonic anhydrase IX (CA9) in patients with hepatocellular carcinoma and patients with cirrhosis

  • 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 serum CA9 levels in HCC and cirrhosis patients. Methods: HCC and cirrhosis patients were prospectively recruited and CA9 levels were determined. 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 hid 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 correlated 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. 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 mainly associated with portal hypertension. Ductular reactions might be a possible source of serum CA9.

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Author:Fabian Finkelmeier, Özge Canli, Kai-Henrik Peiffer, Dirk Walter, Andrea Tal, Christine Koch, Ursula Pession, Johannes Vermehren, Jörg Trojan, Stefan ZeuzemORCiDGND, Albrecht Piiper, Florian Greten, Georgios Grammatikos, Oliver Waidmann
Pubmed Id:
Parent Title (English):PLoS one
Place of publication:Lawrence, Kan.
Contributor(s):Matias A. Avila
Document Type:Article
Year of Completion:2018
Date of first Publication:2018/07/16
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/07/17
Tag:Cirrhosis; Etiology; Hepatocellular carcinoma; Infectious disease epidemiology; Liver diseases; Membrane staining; Negative staining; Portal hypertension
Issue:(7): e0200855
Page Number:16
First Page:1
Last Page:16
Copyright: © 2018 Finkelmeier et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Institutes:Medizin / Medizin
Angeschlossene und kooperierende Institutionen / Georg-Speyer-Haus
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0