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Correlations of microvascular blood flow of contrast-enhanced ultrasound and HGF/c-Met signaling pathway with clinicopathological features and prognosis of patients with hepatocellular carcinoma

Authors Zhuang PH, Xu L, Gao L, Lu W, Ruan LT, Yang J

Received 22 May 2016

Accepted for publication 17 September 2016

Published 14 February 2017 Volume 2017:10 Pages 847—857

DOI https://doi.org/10.2147/OTT.S113353

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 3

Editor who approved publication: Dr Samir Farghaly

Peng-Hui Zhuang,1 Lei Xu,1 Lu Gao,2 Wei Lu,3 Li-Tao Ruan,4 Jin Yang1

1Department of Surgery, 2Department of Internal Medicine, The Hospital of Xi’an Jiao Tong University, 3Department of Gastroenterology, Xi’an First Hospital, 4Department of Ultrasound, The First Affiliated Hospital of Xi’an Jiao Tong University, Xi’an, People’s Republic of China

Abstract: 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.

Keywords: hepatocellular carcinoma, hepatocyte growth factor, cellular-mesenchymal to epithelial transition factor, signaling pathway, microvascular blood flow, contrast-enhanced ultrasound, clinicopathological feature

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