Genomewide gene expression profiles of HPV-positive and HPV-negative oropharyngeal cancer: potential implications for treatment choices.

Genomewide gene expression profiles of HPV-positive and HPV-negative oropharyngeal cancer: potential implications for treatment choices.
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DOI:
10.1001/archoto.2008.540
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发表时间:
2009-02
影响因子:
--
通讯作者:
Chen, Chu
Chen, Chu
中科院分区:
其他
文献类型:
--
作者:
Lohavanichbutr, Pawadee;Houck, John;Fan, Wenhong;Yueh, Bevan;Mendez, Eduardo;Futran, Neal;Doody, David R.;Upton, Melissa P.;Farwell, D. Gregory;Schwartz, Stephen M.;Zhao, Lue Ping;Chen, Chu

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目的研究人乳头瘤病毒(HPV)阳性与阴性口腔鳞状细胞癌(OSCC)中基因表达的差异。我们使用Affytelu 133 plus 2.0芯片检测OSCC和正常口腔组织的基因表达谱。使用PCR和Roche线性阵列HPV基因分型检测法检测HPV DNA,并使用Influenity Pathway Analysis软件(IPA 5.0)分析差异表达基因以检查其潜在的生物学作用。来自119名原发性OSCC患者的肿瘤组织和来自35名非癌症患者的正常口腔组织,所有这些患者都在华盛顿大学附属的三个医疗中心接受治疗。在119例肿瘤中的41例(34.5%)和35例正常组织样本中的2例(5.7%)中发现了HPV DNA,43例HPV中有39例为HPV 16型;口咽癌中HPV DNA的患病率(31例中的23例)高于口腔癌(88例中的18例)。我们发现HPV阳性和HPV阴性口腔癌之间的基因表达没有显着差异,但发现446个探针集(347个已知基因)在HPV阳性和HPV阴性口咽癌之间差异表达。这些基因最重要的功能是DNA复制、DNA修复和细胞周期。HPV阳性和HPV阴性口咽癌之间差异表达的一些基因(例如,TYMS、STMN 1、CCND 1和RBBP 4)参与化疗或放射敏感性。这些结果表明,HPV阳性和HPV阴性口咽癌的生物学差异可能对这些不同肿瘤患者的管理产生影响。
To study the difference in gene expression between human papillomavirus (HPV)-positive and HPV-negative oral squamous cell carcinoma (OSCC). We used Affymetrix U133 plus 2.0 arrays to examine gene expression profiles of OSCC and normal oral tissue. HPV DNA was detected using PCR followed by the Roche Linear Array HPV Genotyping Test, and the differentially expressed genes were analyzed to examine their potential biological roles using the Ingenuity Pathway Analysis Software (IPA 5.0). Tumor tissue from 119 primary OSCC patients and normal oral tissue from 35 patients without cancer, all of whom were treated at three University of Washington-affiliated medical centers. HPV DNA was found in 41 of 119 (34.5%) tumors and 2 of 35 (5.7%) normal tissue samples, with 39 of 43 HPV being HPV type 16; there was a higher prevalence of HPV DNA in oropharyngeal cancer (23 of 31) than in oral cavity cancer (18 of 88). We found no significant difference in gene expression between HPV-positive and HPV-negative oral cavity cancer but found 446 probe sets (347 known genes) differentially expressed between HPV-positive and HPV-negative oropharyngeal cancer. The most prominent functions of these genes are DNA replication, DNA repair, and cell cycle. Some genes differentially expressed between HPV-positive and HPV-negative oropharyngeal cancer (e.g., TYMS, STMN1, CCND1 and RBBP4) are involved in chemotherapy or radiation sensitivity. These results suggest that differences in the biology of HPV-positive and HPV-negative oropharyngeal cancer may have implications for the management of patients with these different tumors.
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