Zhuang Peng-Hui, Xu Lei, Gao Lu, Lu Wei, Ruan Li-Tao, Yang Jin
Department of Surgery.
Department of Internal Medicine, The Hospital of Xi'an Jiao Tong University.
Onco Targets Ther. 2017 Feb 14;10:847-857. doi: 10.2147/OTT.S113353. eCollection 2017.
The study is designed to explore the correlations of microvascular blood flow of contrast-enhanced ultrasound (CEUS) and hepatocyte growth factor (HGF)/c-Met signaling pathway with clinicopathological features and prognosis of patients with hepatocellular carcinoma (HCC). One hundred and eighteen patients pathologically diagnosed as primary HCC were selected. All HCC patients underwent CEUS examination before operation. HCC tissues and adjacent normal tissue specimens were obtained to detect the protein rates of HGF and c-Met expressions by immunohistochemistry. The mRNA expressions of HGF and c-Met were detected by quantitative real-time polymerase chase reaction assay. The microvessel density (MVD) was tested by CD34 immunohistochemistry. Compared with liver parenchyma, the HCC lesions had higher MVD, preoperative peak intensity (PI), area under the curve (AUC), lower preoperative time to peak (TTP), and washout time (WOT). Compared with adjacent normal tissues, the protein and mRNA expressions of HGF were reduced in HCC tissues, but the protein and mRNA expressions of c-Met and MVD were increased. The protein expressions of HGF and c-Met exhibited evident correlations with TNM stage, tumor size, vascular invasion, liver cirrhosis, and hepatitis B virus and hepatitis C virus infection of HCC patients. The tumor size and number, vascular invasion, the protein expressions of HGF and c-Met, and MVD were associated with the TTP, PI, WOT, and AUC of CEUS in HCC patients. The protein expressions of HGF and c-Met, MVD and preoperative PI revealed negative associations with the prognosis of HCC patients. In conclusion, quantitative parameters of CEUS and HGF/c-Met signaling pathway-related proteins may be helpful for early diagnosis and prognosis prediction of HCC patients.
本研究旨在探讨超声造影（CEUS）微血管血流及肝细胞生长因子（HGF）/c-Met信号通路与肝细胞癌（HCC）患者临床病理特征及预后的相关性。选取118例经病理诊断为原发性HCC的患者。所有HCC患者术前均接受CEUS检查。获取HCC组织及癌旁正常组织标本，采用免疫组织化学法检测HGF和c-Met表达的蛋白率。采用定量实时聚合酶链反应检测HGF和c-Met的mRNA表达。通过CD34免疫组织化学检测微血管密度（MVD）。与肝实质相比，HCC病灶的MVD、术前峰值强度（PI）、曲线下面积（AUC）较高，术前达峰时间（TTP）和廓清时间（WOT）较低。与癌旁正常组织相比，HCC组织中HGF的蛋白和mRNA表达降低，但c-Met的蛋白和mRNA表达及MVD增加。HGF和c-Met的蛋白表达与HCC患者的TNM分期、肿瘤大小、血管侵犯、肝硬化以及乙型肝炎病毒和丙型肝炎病毒感染显著相关。肿瘤大小及数量、血管侵犯、HGF和c-Met的蛋白表达以及MVD与HCC患者CEUS的TTP、PI、WOT和AUC相关。HGF和c-Met的蛋白表达、MVD及术前PI与HCC患者的预后呈负相关。综上所述，CEUS定量参数及HGF/c-Met信号通路相关蛋白可能有助于HCC患者的早期诊断及预后预测。
