Lymphatic vessel endothelial hyaluronan receptor‑1 is a novel prognostic indicator for human hepatocellular carcinoma

Kitagawa,Koichi; Nakajima,Go; Kuramochi,Hidekazu; Ariizumi,Shun‑Ichi; Yamamoto,Masakazu

doi:10.3892/mco.2013.167

Lymphatic vessel endothelial hyaluronan receptor‑1 is a novel prognostic indicator for human hepatocellular carcinoma

Authors:
- Koichi Kitagawa
- Go Nakajima
- Hidekazu Kuramochi
- Shun‑Ichi Ariizumi
- Masakazu Yamamoto
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Affiliations: Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Shinjuku‑ku, Tokyo 162-8666, Japan, Department of Chemotherapy and Palliative Care, Tokyo Women's Medical University, Shinjuku‑ku, Tokyo 162-8666, Japan
Published online on: August 6, 2013 https://doi.org/10.3892/mco.2013.167
Pages: 1039-1048

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Abstract

Angiogenesis is an important mechanism of tumor development, growth and metastasis in hepatocellular carcinoma (HCC). The poor prognosis of HCC patients has been associated with a failure to detect recurrences following surgery. In the present study, we investigated the association between the patient characteristics and the expression of angiogenic genes to identify early biomarkers of HCC. A comprehensive angiogenic gene expression profile was obtained by paired TaqMan gene array analysis of primary HCC nodules and adjacent non‑HCC liver tissue from 12 patients. A total of 14 genes were found to be differentially expressed in HCC liver nodules (>2‑fold change); the genes encoding collagen type XVα1, IVα1 and IVα2 were upregulated and the genes associated with vessel growth, neuropilin 2 (NRP2) and lymphatic vessel endothelial hyaluronan receptor‑1 (LYVE‑1) were downregulated. The histopathological analysis revealed that the evolution of HCC nodules from well to poorly differentiated was associated with a 5‑fold decrease in LYVE‑1 expression, reaching its lowest level early during the transition. The significance of this gene as a biomarker of postoperative survival was demonstrated by a 2‑fold decrease in overall survival (OS) rates in the low expression group compared to the high expression group. The multivariate and univariate Cox regression analyses identified LYVE‑1 expression as a significant independent prognostic parameter of OS [hazard ratio (HR)=3.067; 95% confidence interval (CI): 1.507‑6.273; P=0.0021]. Thus, the results of this study suggested that LYVE‑1 expression may constitute a novel early biomarker of postoperative survival in HCC patients.

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