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

Abstract

AbstractBackgroundDespite 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.MethodsThis 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.ResultsAmong 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.ConclusionsThis 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.