Clinicopathological significance of ubiquitin-specific protease 2a (USP2a), fatty acid synthase (FASN), and ErbB2 expression in oral squamous cell carcinomas
Clinicopathological significance of ubiquitin-specific protease 2a (USP2a), fatty acid synthase (FASN), and ErbB2 expression in oral squamous cell carcinomas
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DOI：
10.1016/j.oraloncology.2009.02.004
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发表时间：
2009-10-01
期刊：
影响因子：
4.8
通讯作者：
Graner, Edgard
中科院分区：
文献类型：
--
作者：
da Silva, Sabrina Daniela;Cunha, Isabela Werneck;Graner, Edgard
脂肪酸合成酶（FATIGUE）和ErbB 2在口腔鳞状细胞癌（OSCC）中的过表达已被描述。脂肪酶是负责内源性脂肪酸合成的关键脂肪生成酶，其表达可由ErbB 2调节。去泛素化酶（DUB）泛素特异性蛋白酶2a（USP 2a）通过稳定FcB蛋白在前列腺癌细胞存活中起关键作用。本研究旨在探讨口腔鳞状细胞癌中FXR、ErbB 2和USP 2a的基因表达和免疫组化状态是否与口腔鳞状细胞癌的临床病理特征相关。在激光捕获显微切割的OSCC样本中，通过qRT-PCR观察到ErbB 2、FXR和USP 2a表达之间存在强正相关性（p = 0.001）。神经浸润与ErbB 2 mRNA表达相关（p = 0.046）。转移性颈淋巴结的存在与FXR（p = 0.002）、ErbB 2（p = 0.001）和USP 2a（p = 0.006）mRNA水平相关。ErbB 2在高分化病变中细胞膜染色较强，而在低分化肿瘤中发现胞浆阳性。大多数对FXR高阳性的OSCC（97.06%）也在细胞膜上标记了ErbB 2（p = 0.001）。FXR和ErbB 2阳性与肿瘤厚度和淋巴管栓塞相关（分别为p = 0.006和p = 0.035，p = 0.006和p = 0.024）。ErbB 2的膜表达以及Fas和Ki-67染色与高复发风险显著相关，（对数秩检验，分别为p = 0.0056、p = 0.0011和p = 0.0004）和总生存期（对数秩检验，分别为p = 0.0005、p = 0.0062和p = 0.0001）。综上所述，本研究的结果提示，在口腔鳞状细胞癌中，FXR、ErbB 2和USP 2a之间存在分子联系，因为它们的mRNA和蛋白水平与肿瘤进展和不良预后相关。(C)2009爱思唯尔有限公司保留所有权利。
Overexpression of fatty acid synthase (FASN) and ErbB2 has been described in oral squamous cell carcinomas (OSCC). FASN is the key lipogenic enzyme responsible for the endogenous synthesis of fatty acids and its expression can be regulated by ErbB2. The deubiquitinating enzyme (DUB) ubiquitin-specific protease 2a (USP2a) plays a critical role in prostate cancer cell survival by stabilizing the FASN protein. This study investigates whether the gene expression and the immunohistochemical status of FASN, ErbB2, and USP2a correlate with the clinicopathological characteristics of OSCC cases. A strong positive correlation among ErbB2, FASN, and USP2a expression (p = 0.001) was observed by qRT-PCR in laser capture micro-dissected OSCC samples. Perineural infiltration was associated with ErbB2 mRNA expression (p = 0.046). The presence of metastatic cervical lymph nodes was associated with FASN (p = 0.002), ErbB2 (p = 0.001), and USP2a (p = 0.006) mRNA levels. ErbB2 staining at the cell membranes was stronger in well-differentiated lesions while a cytoplasmic positivity was found in poorly differentiated tumors. Most of the OSCC (97.06%) that showed a high positivity for FASN were also labeled for ErbB2 at the cell membranes (p = 0.001). FASN and ErbB2 positivity was associated with tumor thickness and lymphatic embolization (p = 0.006 and p = 0.035, p = 0.006 and p = 0.024 respectively). The membrane expression of ErbB2 as well as FASN and Ki-67 staining were significantly associated with a high risk of recurrence by predicting both disease free survival (log-rank test, p = 0.0056, p = 0.0011, and p = 0.0004, respectively) and overall survival (log-rank test, p = 0.0005, p = 0.0062, and p = 0.0001, respectively). Taken together, the results presented here suggest a molecular connection among FASN, ErbB2, and USP2a in OSCC since their mRNA and protein levels were associated with tumor progression and poor prognosis. (C) 2009 Elsevier Ltd. All rights reserved.