Blood reelin in the progression of chronic liver disease

Adv Med Sci. 2021 Mar;66(1):148-154. doi: 10.1016/j.advms.2021.01.006. Epub 2021 Feb 6.

Abstract

Purpose: Reelin is an extracellular matrix protein originally found to be associated with neuropsychiatric disorders. Recent findings indicate, that reelin may also play an important role in the process of liver fibrosis as well as in the development of hepatocellular carcinoma (HCC). Against this background, the aim of our study was to explore alterations in blood reelin levels in different stages of chronic liver diseases.

Patients and methods: We analyzed blood samples of patients with chronic liver disease without liver fibrosis (n ​= ​25), with liver fibrosis (n ​= ​36), with liver cirrhosis (n ​= ​74), with HCC (n ​= ​26) as well as of healthy controls (n ​= ​15). Blood reelin concentrations were determined utilizing an enzyme-linked immunosorbent assay.

Results: Blood reelin levels were significantly elevated in patients who had liver fibrosis or cirrhosis compared to patients without liver fibrosis and healthy controls (13.9 (10.2-21.1) ng/ml vs. 11.2 (8.8-16.8) ng/ml, p ​= ​0.032). Importantly, patients with HCC displayed significantly higher reelin concentrations compared to patients with liver cirrhosis alone (27.0 (17.3-35.9) ng/ml vs. 16.6 (11.0-22.7) ng/ml, p ​< ​0.001). Blood reelin was not relevantly linked to liver function, inflammation and etiology of liver disease.

Conclusions: Our results demonstrate, that blood reelin levels are altered in different stages of chronic liver disease, which makes reelin a potential biomarker in this setting. This may be especially relevant with regard to its use as an additional tumor marker of HCC.

Keywords: Cirrhosis; Hepatocellular carcinoma; Liver fibrosis; Reelin.

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood*
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / epidemiology
  • Carcinoma, Hepatocellular / pathology*
  • Case-Control Studies
  • Cell Adhesion Molecules, Neuronal / blood*
  • Disease Progression
  • Extracellular Matrix Proteins / blood*
  • Female
  • Follow-Up Studies
  • Germany / epidemiology
  • Humans
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / epidemiology
  • Liver Cirrhosis / pathology*
  • Liver Neoplasms / blood
  • Liver Neoplasms / epidemiology
  • Liver Neoplasms / pathology*
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / blood*
  • Prognosis
  • Reelin Protein
  • Serine Endopeptidases / blood*
  • Survival Rate

Substances

  • Biomarkers
  • Cell Adhesion Molecules, Neuronal
  • Extracellular Matrix Proteins
  • Nerve Tissue Proteins
  • Reelin Protein
  • RELN protein, human
  • Serine Endopeptidases