The expression and prognostic significance of hepatoma-derived growth factor in oral cancer
The expression and prognostic significance of hepatoma-derived growth factor in oral cancer
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DOI：
10.1016/j.oraloncology.2012.01.014
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发表时间：
2012-07-01
期刊：
影响因子：
4.8
通讯作者：
Tai, Ming-Hong
中科院分区：
文献类型：
--
作者：
Lin, Yu-Wei;Li, Chien-Feng;Tai, Ming-Hong
肝癌衍生生长因子（HDGF）参与致癌进展，并代表了几种类型癌症的预后因素。本研究旨在阐明HDGF在口腔癌发生过程中的作用。通过免疫印迹、侵袭实验和集落形成实验研究HDGF在人口腔癌细胞系中的表达及其致瘤性。采用重组腺病毒载体调节口腔癌细胞中HDGF的水平。使用组织芯片（TMA）的免疫组化分析，包括手术切除的样本从95例口腔癌患者进行描绘HDGF表达和临床病理参数之间的相关性。HDGF在恶性口腔癌细胞中的表达高于良性口腔癌细胞。腺病毒介导的HDGF过表达和基因敲减表明细胞HDGF水平调节口腔癌细胞的致瘤行为。免疫组化分析显示HDGF在口腔癌组织的细胞核和细胞质中表达增加。HDGF核表达与肿瘤分期（P = 0.004）和分级（P = 0.013）显著相关，而胞浆表达与肿瘤坏死相关（P = 0.002）。Kaplan-Meier分析显示，核HDGF高表达的患者的5年疾病特异性生存率（P = 0.0069）、无转移生存率（P = 0.0168）和局部无复发生存率（P = 0.0047）显著更差。多因素分析表明，核HDGF标记指数是疾病特异性和局部无复发生存的独立预后因素。HDGF的过度表达有助于口腔癌细胞的致癌过程，并构成了口腔癌患者生存结局的一个新的预后因素。(C)2012爱思唯尔有限公司保留所有权利。
Hepatoma-derived growth factor (HDGF) participates in oncogenic progression and represents a prognostic factor in several types of cancer. This study aimed to elucidate the role of HDGF during oral carcinogenesis. HDGF expression and the tumorigenic behaviors in human oral cell lines were investigated by immunoblotting, invasion and colony formation assays. Recombinant adenovirus vectors were employed to modulate the HDGF level in oral cancer cells. Immunohistochemical analysis using tissue microarray (TMA) consisting of surgically resected samples from 95 oral cancer patients was performed to delineate the correlation between HDGF expression and clinic-pathological parameters. HDGF expression was higher in malignant oral cancer cells than benign ones. Adenovirus-mediated HDGF overexpression and knockdown demonstrated the cellular HDGF level regulated the tumorigenic behaviors of oral cancer cells. Immunohistochemical analysis revealed increased HDGF expression in the nucleus and cytoplasm in oral cancer tissues. The nuclear HDGF expression was significantly correlated with tumor stage (P = 0.004) and grade (P = 0.013) while the cytoplasmic HDGF expression was associated with tumor necrosis (P = 0.002). Kaplan-Meier analysis revealed that patients with high nuclear HDGF expression had significantly worse 5-year disease-specific survival (P = 0.0069), metastasis-free survival (P = 0.0168), and local recurrence-free survival (P = 0.0047). Multivariate analysis indicated that the nuclear HDGF labeling index was an independent prognostic factor for disease-specific and local recurrence-free survival. HDGF overexpression contributes to the oncogenic processes in oral cancer cells and constitutes a novel prognostic factor for survival outcome of oral cancer patients. (C) 2012 Elsevier Ltd. All rights reserved.