Abstract
BackgroundTie2-expressing monocytes (TEMs) are found in various tumors, involved in forming tumor blood vessels and expressing several important proangiogenic factors. The goals of this study were to evaluate the value of TEMs in diagnosing and predicting the prognosis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).MethodsFlow cytometry was performed to identify and count TEMs in peripheral blood monocytes from HCC patients (n = 84) receiving hepatectomy, HBV cirrhotic patients (n = 21), benign tumors patients (n = 15) and healthy volunteers (n = 23). Angiopoietin-2 (Ang-2) levels in the plasma were determined by enzyme linked immunosorbent assay. The distribution of TEMs in tumor tissue was observed by immunofluorescence staining. Then we determined the vascular area as a percentage of tumor area (vascular area/tumor area) by immunohistochemical staining. Finally the prognostic significance of TEMs and other clinicopathologic factors was evaluated.ResultsPercentage of TEMs in peripheral blood monocytes significantly increased in HCC patients compared with HBV cirrhotic patients and healthy donors (both P< 0.001). However there was no significance in benign liver tumor (P = 0.482). In addition, the percentage of circulating TEMs was positively correlated with plasma Ang-2 concentration (P<0.001, r2 = 0.294) and vascular area/tumor area (P<0.001, r2 = 0.126). Furthermore the percentage of intratumoral TEMs was significantly higher than that of paratumoral TEMs (P<0.001). Increased circulating TEMs was associated with poor overall survival (P = 0.043) and a shorter time to recurrence (P = 0.041). Multivariate Cox analysis also revealed that the percentage of TEMs in peripheral blood was an independent factor for HCC patients’ prognosis.ConclusionsTEMs may promote angiogenesis in HCC regarding the angiopoietin/Tie2 signal pathway. Percentage of TEMs in peripheral blood monocytes may be applied as a biomarker for identifying HBV-related HCC and predicting the prognosis of these patients after resection.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world
Percentage of Tie2-expressing monocytes (TEMs) in peripheral blood monocytes significantly increased in hepatocellular carcinoma (HCC) patients compared with hepatitis B virus (HBV) cirrhotic patients and healthy donors
Percentage of TEMs in peripheral blood monocytes may be applied as a biomarker for identifying HBV-related HCC and predicting the prognosis of these patients after resection
Summary
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. HCC is one of the most abundant vascular solid tumors, in the formation and growth of which angiogenesis plays an important role. Tie2-expressing monocytes (TEMs) have been found in various human tumors, to form tumor blood vessels and express several proangiogenic factors such as basic fibroblast growth factor (b-FGF), vascular endothelial growth factor (VEGF), and matrix metalloproteinase-9 (MMP-9) [3,4,5]. Tie2-expressing monocytes (TEMs) are found in various tumors, involved in forming tumor blood vessels and expressing several important proangiogenic factors. The goals of this study were to evaluate the value of TEMs in diagnosing and predicting the prognosis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC)
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