Macrophage activation marker soluble CD163 may predict disease progression in hepatocellular carcinoma

Abstract

Background: Tumor associated macrophages are present in hepatocellular carcinoma (HCC) and associated with a poor prognosis. The aim of the present study was to investigate the levels and dynamics of soluble (s)CD163, a specific macrophage activation marker, in patients with HCC. Methods: In a cohort from Australia, we studied 109 HCC patients, 116 patients with chronic liver disease (CLD), and 52 healthy controls. We examined associations between baseline sCD163 and parameters of HCC severity as well as overall and progression-free survival. In a cohort of 42 Danish HCC patients, we measured sCD163 at baseline and 1, 4 and 12 weeks after ablative treatment. Results: In the Australian cohort, median sCD163 was similarly increased in HCC (5.6[interquartile range 3.5–8.0] mg/L) and CLD (6.1[3.6–9.6] mg/L) patients as compared to controls (2.0[1.5–2.7] mg/L, p < 0.001). sCD163 correlated with Child-Pugh and MELD scores in both HCC and CLD patients. Patients with high sCD163 levels had shorter progression-free survival (p < 0.001), but not overall survival (p = 0.15). In the Danish cohort, patients with HCC progression at 12 weeks had an increase in sCD163. There was no association between sCD163 and HCC size, number, vascular invasion or metastasis in any of the cohorts. Conclusions: We confirmed increased sCD163 levels in CLD and HCC patients associated with Child-Pugh and MELD scores and portal hypertension, but not with HCC size and number, or metastasis. As a novel finding, baseline sCD163 appeared to predict a rapid HCC progression, as sCD163 increased during follow-up in HCC patients who showed progression.

KeyWords:

• Biomarker
• immunity
• inflammation
• liver disease
• prediction
• tumor associated macrophages

Acknowledgements

The authors wish to thank Kirsten Bank Petersen, Department of Clinical Biochemistry, Aarhus University Hospital, for excellent technical assistance.

Statement of interests

1. Aarhus University and HJM have received royalties from IQ-products, who sell ELISA kits for sCD163 measurement. A different kit was used in the present study, and the study was not supported by IQ-products in any way. (IQ-products: Rozenburglaan 13a, 9727 DL Groningen, Netherlands. Tel: [phone]. http://www.iqproducts.nl).

2. Aarhus University in collaboration with KK, HJM and HG has filed patent applications for the use of sCD163 as a biomarker. (Aarhus University: Nordre Ringgade 1, 8000 Aarhus C, Denmark. Tel: [phone]. http://www.au.dk).

Financial support

The NOVO Nordisk Foundation, The Danish Strategic Research Council (10-092797) and “Savværksejer Jeppe Juhl og hustru Ovita Juhls mindelegat”.

Declaration of interest

The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.