Fundamental differences in cell cycle deregulation in human papillomavirus-positive and human papillomavirus-negative head/neck and cervical cancers
Fundamental differences in cell cycle deregulation in human papillomavirus-positive and human papillomavirus-negative head/neck and cervical cancers
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DOI：
10.1158/0008-5472.can-06-3619
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发表时间：
2007-05-15
期刊：
影响因子：
11.2
通讯作者：
Ahlquist, Paul
中科院分区：
文献类型：
--
作者：
Pyeon, Dohun;Newton, Nlichael A.;Ahlquist, Paul
人乳头瘤病毒（RPV）与几乎所有的宫颈癌，20%至30%的头颈癌（HNC）和其他癌症有关。由于HNC也出现在HPV阴性患者中，因此这种类型的癌症提供了独特的机会来定义在相同组织中出现的HPV阳性与HPV阴性癌症的相似性和差异。在这里，我们描述了84个HNC，宫颈癌和位点匹配的正常上皮细胞样本的全基因组表达谱，其中我们使用激光捕获显微切割来富集肿瘤源性与正常上皮细胞的样本。该分析显示，HPV+ HNC和宫颈癌的基因表达模式不同，但与HPV-HNC相比有许多共同的变化。其中一些共同的变化被预测到了，但其他许多变化却没有。值得注意的是，发现HPV+ HNC和宫颈癌在其细胞周期基因的不同和更大子集的表达方面比在HPV-HNC中观察到的表达上调。此外，HPV+癌症过度表达通常仅在减数分裂细胞中表达的睾丸特异性基因。HPV+ HNC和HPV-HNC之间的许多（尽管不是全部）标志性差异是HPV的直接结果，特别是病毒E6和E7癌基因。这包括HPV癌基因与睾丸特异性基因表达的新关联。这些在原发性人类肿瘤中的发现为HPV+和HPV-癌症的早期检测提供了新的生物标志物，并强调了靶向E6和E7功能单独或与放射和/或传统化疗组合在HPV+癌症治疗中的潜在价值。
Human papillomaviruses (RPV) are associated with nearly all cervical cancers, 20% to 30% of head and neck cancers (HNC), and other cancers. Because HNCs also arise in HPV-negative patients, this type of cancer provides unique opportunities to define similarities and differences of HPV-positive versus HPV-negative cancers arising in the same tissue. Here, we describe genome-wide expression profiling of 84 HNCs, cervical cancers, and site-matched normal epithelial samples in which we used laser capture microdissection to enrich samples for tumor-derived versus normal epithelial cells. This analysis revealed that HPV+ HNCs and cervical cancers differed in their patterns of gene expression yet shared many changes compared with HPV- HNCs. Some of these shared changes were predicted, but many others were not. Notably, HPV+ HNCs and cervical cancers were found to be up-regulated in their expression of a distinct and larger subset of cell cycle genes than that observed in HPV- HNC. Moreover, HPV+ cancers overexpressed testis-specific genes that are normally expressed only in meiotic cells. Many, although not all, of the hallmark differences between HPV+ HNC and HPV- HNC were a direct consequence of HPV and in particular the viral E6 and E7 oncogenes. This included a novel association of HPV oncogenes with testis-specific gene expression. These findings in primary human tumors provide novel biomarkers for early detection of HPV+ and HPV- cancers, and emphasize the potential value of targeting E6 and E7 function, alone or combined with radiation and/or traditional chemotherapy, in the treatment of HPV+ cancers.