Tie2-Expressing Monocytes Are Associated with Identification and Prognoses of Hepatitis B Virus Related Hepatocellular Carcinoma after Resection.
Tie2-Expressing Monocytes Are Associated with Identification and Prognoses of Hepatitis B Virus Related Hepatocellular Carcinoma after Resection.
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DOI：
10.1371/journal.pone.0143657
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Zhou J
中科院分区：
文献类型：
--
作者：
He YF;Wang CQ;Yu Y;Qian J;Song K;Sun QM;Zhou J
Tie 2表达单核细胞（TEM）存在于多种肿瘤中，参与形成肿瘤血管并表达几种重要的促血管生成因子。本研究的目的是评价TEM在诊断和预测B型肝炎病毒（HBV）相关性肝细胞癌（HCC）预后中的价值。采用流式细胞术对接受肝切除术的HCC患者（n = 84）、HBV感染患者（n = 21）、良性肿瘤患者（n = 15）和健康志愿者（n = 23）的外周血单核细胞中的TEM进行鉴定和计数。酶联免疫吸附法测定血浆血管生成素-2（Ang-2）水平。免疫荧光染色观察TEM在肿瘤组织中的分布。然后，我们通过免疫组织化学染色确定血管面积占肿瘤面积的百分比（血管面积/肿瘤面积）。最后，TEM和其他临床病理因素的预后意义进行了评估。肝癌患者外周血单核细胞TEM阳性率明显高于HBV感染者和健康献血员（P均< 0.001）。而在良性肝肿瘤中无显著性差异（P = 0.482）。此外，TEMs的百分比与血浆Ang-2浓度（P<0.001，r2 = 0.294）和血管面积/肿瘤面积（P<0.001，r2 = 0.126）呈正相关。肿瘤内TEMs所占比例明显高于瘤旁TEMs（P<0.001）。循环TEM增加与总生存率差（P = 0.043）和复发时间短（P = 0.041）相关。多因素考克斯分析显示外周血TEM百分比是影响肝癌患者预后的独立因素。TEM可能通过促血管生成素/Tie 2信号通路促进HCC中的血管生成。外周血单核细胞中TEM的百分比可作为识别HBV相关HCC和预测切除术后预后的生物标志物。
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). Flow 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. Percentage 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. TEMs 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.