Vitamin B₁₂ and its binding proteins in hepatocellular carcinoma and chronic liver diseases

Abstract

Background. The vitamin B₁₂ (B₁₂)-binding protein haptocorrin (HC) has proven to be a potentially useful biomarker in patients with fibrolamellar hepatocellular carcinoma (HCC). Little is known concerning the level of HC and other B₁₂-related proteins in patients with HCC as compared to patients with other chronic liver diseases (CLDs) and healthy controls. We hypothesized that HC could be a biomarker of HCC. Aims. To investigate levels of HC and B₁₂-related proteins in HCC compared to CLDs and healthy controls. Methods. We investigated two patient populations: A cross-sectional cohort of HCC patients (n = 130), CLD patients (n = 102) and healthy controls (n = 46) and a cohort of 38 HCC patients studied at baseline and 1, 4, and 12 weeks following ablative treatment. Patients were evaluated by standard biochemistry, Child–Pugh-score and Barcelona Clinic Liver Cancer (BCLC) classification. We analyzed total B₁₂ by routine methods and HC, transcobalamin (TC), B₁₂ saturated TC (holoTC), and the soluble cell surface receptor for holoTC (sCD320) by in-house enzyme-linked immunosorbent assay. Results. HC showed higher median (range) levels for both HCC (590 [290–5860]) and CLD patients (620 [310–4010]) compared to controls (460 [250–2020]) (p < 0.01). Total B₁₂, TC, holoTC, and sCD320 showed elevated levels in both HCC and CLD compared to controls. Only holoTC changed following treatment, without a concurrent change in TC. Conclusion. B₁₂ and B₁₂-related proteins (total B₁₂, HC, TC, holoTC, and sCD320) show elevations in both HCC and CLD patients compared to controls, suggesting a relation to CLD in general rather than to primary liver cancer. Thus, HC is not useful as a biomarker for HCC.

Key Words::

• biomarker
• chronic liver disease
• haptocorrin
• hepatocellular carcinoma
• holo transcobalamin
• soluble cell surface receptor 320 of holo transcobalamin
• transcobalamin
• vitamin B₁₂

Acknowledgments

The authors acknowledge the technical assistance of Anna Lisa Christensen, Inger Marie Jensen and Jette Fisker Pedersen. This study was supported by the NOVO Nordisk Foundation, the Danish Cancer Society (Kræftens Bekæmpelse) and the Lundbeck foundation. The content of the article has not been influenced by the sponsors.

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