Martinez Ivan, Wang Jun, Hobson Kenosha F, Ferris Robert L, Khan Saleem A
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Room East 1240, 200 Lothrop Street, Pittsburgh, PA 15208, USA.
Eur J Cancer. 2007 Jan;43(2):415-32. doi: 10.1016/j.ejca.2006.09.001. Epub 2006 Oct 31.
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.
人乳头瘤病毒（HPV）与头颈部鳞状细胞癌（SCCHN）的一部分发病机制有关。本研究的目的是比较HPV阳性和HPV阴性口咽癌与正常口腔上皮细胞的基因表达谱。使用Affymetrix人类U133A基因芯片，我们的结果显示，与正常口腔上皮相比，397个基因在HPV阳性SCCHN中差异表达。上调的基因包括参与细胞周期调控（CDKN2A）、细胞分化（SFRP4）和DNA修复（RAD51AP1）的基因，而下调的基因包括参与蛋白水解（PRSS3）的基因。我们还发现，与正常口腔黏膜相比，HPV阴性SCCHN中有162个差异表达基因。上调的基因包括参与细胞增殖（AKR1C3）和转录调控（SNAPC1）的基因，而下调的基因包括参与细胞凋亡（CLU）和RNA加工（RBM3）的基因。我们的研究还确定了与HPV阴性SCCHN和正常口腔组织相比，HPV阳性SCCHN中有59个差异表达基因的亚组。这些上调的基因包括参与核结构和减数分裂（SYCP2）、DNA修复（RFC5）和转录调控（ZNF238）的基因。发现参与蛋白水解（KLK8）和信号转导（CRABP2）的基因在HPV阳性SCCHN中下调。通过对一些代表性基因进行定量实时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阴性口咽鳞状细胞癌中特定的基因表达模式，这些模式可能作为SCCHN发展的潜在生物标志物。
