Tie-2 Expressing Monocytes in Hepatitis C Virus Related Hepatocellular Carcinoma

Abstract

Angiogenesis is a critical step in the development and progression of hepatocellular carcinoma (HCC). Tie-2-expressing monocytes (TEMs) with pro-angiogenic activity are recruited to tumor site where they stimulate tumor angiogenesis. Objective: This study aimed to assess the role of TEMs in diagnosis of hepatitis C virus (HCV)-related HCC. Methods: The study was conducted on Fifty patients diagnosed with HCC and HCV. Patients were categorized into two groups: one included patients with HCC (n=25) and the other included HCV patients (n=25). Twenty-five age and sex matched healthy individuals were recruited as a control group. The frequency of TEMs, as defined as CD14+CD16+Tie-2+ cells, in the peripheral blood was determined by flow cytometry. Results: The frequency of TEMs in PB monocytes was significantly higher in HCC group (53.1±18.2%) than in patients with HCV (27.3±13.9%) and controls (8.4±3.9%). TEMs percentage correlates with advanced Child-Pugh stage in HCC and HCV patients (P<0.01). Upon performing ROC curve analysis, a cut off point of 33% for TEMs was able to differentiate HCC patients from HCV-infected patients. As regard differentiating HCC patients from healthy subjects the cut off value of 33.8% yielded 88% sensitivity and 100% specificity. The diagnostic performance of combination of TEMs and AFP was also assessed with 98% sensitivity and 100% specificity. Conclusion: Percentage of TEMs in PB monocytes may be applied as a complementary biomarker for identifying HCV-related HCC along with AFP. Inhibiting the proangiogenic functions of TEMs may represent a promising strategy to improve the efficacy of current treatments for HCC.