Increased plasma levels of monocyte chemoattractant protein-1 in patients with hepatitis B virus pre-S2 gene deletion mutation predict a higher risk of hepatocellular carcinoma recurrence after curative surgical resection

Cancer. 2023 Sep 1;129(17):2621-2636. doi: 10.1002/cncr.34815. Epub 2023 Apr 25.

Abstract

Background: Despite resection surgery as a curative therapy for hepatocellular carcinoma (HCC), the high rate of postoperative HCC recurrence remains a big challenge for patient survival. Chronic hepatitis B virus (HBV) infection is the most important risk factor for HCC. Deletion mutation in the HBV pre-S2 gene leads to expression of an essential viral oncoprotein called pre-S2 mutant and represents an independent prognostic biomarker for HCC recurrence after curative surgical resection. Additionally, cytokines are multifunctional secreted proteins and implicated in all stages of HBV-related HCC tumorigenesis.

Methods: This study aimed to identify the cytokines whose plasma levels were associated with pre-S2 gene deletion mutation and HCC recurrence and evaluate their potential to be combined with pre-S2 gene deletion mutation in predicting HCC recurrence.

Results: Among a panel of 27 cytokines examined, plasma levels of monocyte chemoattractant protein-1 (MCP-1) were significantly upregulated in patients with pre-S2 gene deletion mutation or HCC recurrence. MCP-1 was validated as an independent prognostic biomarker for HCC recurrence. Moreover, patients with both the presence of pre-S2 gene deletion mutation and high levels of MCP-1 displayed a higher risk of HCC recurrence than patients with either one or none of these two biomarkers. The combination of pre-S2 gene deletion mutation and MCP-1 levels exhibited a better prognostic performance for HCC recurrence than each biomarker alone.

Conclusions: This study discovered that MCP-1 levels had a significance to be as a combination biomarker with pre-S2 gene deletion mutation providing an improved performance in predicting HCC recurrence after curative surgical resection.

Keywords: hepatitis B virus; hepatocellular carcinoma; monocyte chemoattractant protein-1; pre-S2 gene deletion mutation; recurrence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / surgery
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Gene Deletion
  • Hepatitis B Surface Antigens / genetics
  • Hepatitis B Surface Antigens / metabolism
  • Hepatitis B virus / genetics
  • Hepatitis B*
  • Hepatitis B, Chronic* / complications
  • Hepatitis B, Chronic* / genetics
  • Hepatitis B, Chronic* / pathology
  • Humans
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / pathology
  • Liver Neoplasms* / surgery
  • Mutation

Substances

  • Chemokine CCL2
  • Hepatitis B Surface Antigens
  • CCL2 protein, human