Combination of serum paraoxonase/arylesterase 1 and antithrombin-III is a promising non-invasion biomarker for discrimination of AFP-negative HCC versus liver cirrhosis patients

Clin Res Hepatol Gastroenterol. 2021 Sep;45(5):101583. doi: 10.1016/j.clinre.2020.11.013. Epub 2021 Mar 21.

Abstract

Objective: α-fetoprotein is often used in the diagnosis of hepatocellular carcinoma (HCC). However, there are currently less efficient and highly specific biomarkers to distinguish AFP-negative HCC from liver cirrhosis (LC) patients.

Patients and methods: We retrospectively analyzed the data of patients who were treated in our hospitals. iTRAQ coupled with mass spectrometry was used to identify candidate serum proteins in a discovery set (n = 36) including AFP-negative HCC and LC patients. After Western blot detection, potential serum biomarkers were confirmed using ELISA in a validation set (n = 90). The diagnostic performance of the selected proteins was assessed using receiver operating characteristic (ROC).

Results: PON1 and ATIII were selected as target proteins and were significantly higher in LC than those in AFP-negative HCC patients as validated by Western blot and ELISA, which was consistent with the result of iTRAQ. The AUC was 0.848 as PON1 and ATIII were combined (sensitivity: 80.0%; specificity: 73.3%), and performed much better than that of a single biomarker.

Conclusion: These findings suggest that PON1 and ATIII have the potential to serve as effective biomarkers for distinguishing AFP-negative HCC from cirrhosis.

Keywords: AFP-negative hepatocellular carcinoma; ATIII; Biomarker; Diagnostic; PON1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antithrombins* / blood
  • Aryldialkylphosphatase* / blood
  • Biomarkers / blood
  • Carcinoma, Hepatocellular* / blood
  • Carcinoma, Hepatocellular* / diagnosis
  • Humans
  • Liver Cirrhosis* / blood
  • Liver Cirrhosis* / diagnosis
  • Liver Neoplasms* / blood
  • Liver Neoplasms* / diagnosis
  • Retrospective Studies
  • alpha-Fetoproteins / metabolism

Substances

  • Antithrombins
  • Biomarkers
  • alpha-Fetoproteins
  • Aryldialkylphosphatase