Identification of differentially expressed genes in HPV-positive and HPV-negative oropharyngeal squamous cell carcinomas
Identification of differentially expressed genes in HPV-positive and HPV-negative oropharyngeal squamous cell carcinomas
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DOI：
10.1016/j.ejca.2006.09.001
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发表时间：
2007-01-01
影响因子：
8.4
通讯作者：
Khan, Saleem A.
中科院分区：
文献类型：
--
作者：
Martinez, Ivan;Wang, Jun;Khan, Saleem A.
人类乳头瘤病毒(HPV)与头颈部鳞状细胞癌(SCCHN)的发病机制有关。本研究的目的是比较HPV阳性和HPV阴性的口咽癌与正常口腔上皮的细胞基因表达谱。利用Affymetrix Human U133A基因芯片，我们的结果显示，在HPV阳性的SCCHN中，有397个基因与正常口腔上皮相比有差异表达。上调的基因包括与细胞周期调控(CDKN2A)、细胞分化(SFRP4)和DNA修复(RAD51AP1)相关的基因，而下调的基因包括与蛋白分解相关的基因(PRSS3)。我们还发现了162个HPV阴性的SCCHN与正常口腔黏膜相比的差异表达基因。上调的基因包括与细胞增殖(AKR1C3)和转录调控(SNAPC1)相关的基因，下调的基因包括与细胞凋亡(CLU)和RNA加工(RBM3)相关的基因。我们的研究还发现，与HPV阴性的SCCHN和正常口腔组织相比，HPV阳性的SCCHN中有59个差异表达基因。这些上调的基因包括与核结构和减数分裂(SYCP2)、DNA修复(RFC5)和转录调控(ZNF238)有关的基因。在HPV阳性的SCCHN中，参与蛋白分解(KLK8)和信号转导(CRABP2)的基因表达下调。通过对几个代表性基因的实时定量RT-PCR分析，验证了基因芯片实验的结果。我们的结果揭示了HPV阳性和HPV阴性的口咽鳞癌中特定的基因表达模式，这可能是SCCHN发生的潜在生物标志物。(C)2006爱思唯尔有限公司。保留所有权利。
Human papillomaviruses (HPVs) have been implicated in the pathogenesis of a subset of squamous cell carcinoma of the head and neck (SCCHN). The goal of this study was to compare the cellular gene expression profiles of HPV-positive and HPV-negative oropharyngeal carcinomas with those of the normal oral epithelium. Using Affymetrix Human U133A GeneChip, our results showed that 397 genes were differentially expressed in HPV-positive SCCHN compared to the normal oral epithelium. The upregulated genes included those involved in cell cycle regulation (CDKN2A), cell differentiation (SFRP4) and DNA repair (RAD51AP1), while the downregulated genes included those involved in proteolysis (PRSS3). We also found 162 differentially expressed genes in HPV-negative SCCHN compared to the normal oral mucosa. The upregulated genes included those involved in cell proliferation (AKR1C3) and transcription regulation (SNAPC1), while downregulated genes included those involved in apoptosis (CLU) and RNA processing (RBM3). Our studies also identified a subgroup of 59 differentially expressed genes in HPV-positive SCCHN as compared to both HPV-negative SCCHN and normal oral tissues. Such upregulated genes included those involved in nuclear structure and meiosis (SYCP2), DNA repair (RFC5), and transcription regulation (ZNF238). Genes involved in proteolysis (KLK8) and signal transduction (CRABP2) were found to be downregulated in HPV-positive SCCHN. The results of GeneChip experiments were validated by quantitative real-time RT-PCR analysis of a few representative genes. Our results reveal specific gene expression patterns in HPV-positive and HPV-negative oropharyngeal squamous carcinomas that may serve as potential biomarkers for the development of SCCHN. (c) 2006 Elsevier Ltd. All rights reserved.