Proteomic analysis of oropharyngeal carcinomas reveals novel HPV-associated biological pathways.
Proteomic analysis of oropharyngeal carcinomas reveals novel HPV-associated biological pathways.
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DOI：
10.1002/ijc.27699
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发表时间：
2013-02-01
影响因子：
6.4
通讯作者：
Liebler, Daniel C.
中科院分区：
文献类型：
--
作者：
Slebos, Robbert J. C.;Jehmlich, Nico;Brown, Brandee;Yin, Zhirong;Chung, Christine H.;Yarbrough, Wendell G.;Liebler, Daniel C.
口咽癌（OPC）可分为两个同样流行的亚型，这取决于是否存在人乳头瘤病毒（HPV）。HPV阳性（HPV+）OPC患者代表了一个独特的队列，与HPV阴性（HPV-）OPC相比，具有不同的肿瘤生物学和临床行为。遗传学研究表明，染色体和基因表达的变化与OPC的不同亚类，虽然HPV感染的蛋白质组学后果是未知的。我们使用标准化的全球蛋白质组学分析平台分析了10例HPV+和10例HPV− OPCs以及10例正常成人口腔上皮。该分析总共产生了2，653种可靠鉴定的蛋白质，我们根据HPV+，HPV-和正常上皮之间的表达差异选择了31种蛋白质用于靶向蛋白质定量。HPV状态差异表达蛋白的分析显示，HPV-OPC中涉及上皮细胞发育、角化和细胞外基质组织的蛋白质富集，而HPV+ OPC中发现DNA起始和复制以及细胞周期控制中的蛋白质富集。对转录因子靶点的富集分析鉴定了在HPV+ OPC中高度表达的转录因子E2 F1和E2 F4。我们还发现在HPV+ OPC中高表达的乙酰氨基琥珀酸合酶1（ASS 1）表明HPV+ OPC更依赖于条件必需氨基酸精氨酸，并且这在OPC特异性组织微阵列上得到证实。这些确定的蛋白质组变化揭示了HPV+和HPV− OPC的新驱动分子途径，可能与OPC的治疗策略和结局有关。
Oropharyngeal carcinoma (OPC) can be classified into two equally prevalent sub-types depending on the presence of Human Papillomavirus (HPV). Patients with HPV-positive (HPV+) OPC represent a unique cohort with a distinct tumor biology and clinical behavior compared to HPV-negative (HPV-) OPC. Genetic studies have demonstrated chromosomal and gene expression changes associated with distinct sub-classes of OPC, although the proteomic consequences of HPV infection are not known. We analyzed sets of 10 HPV+ and 10 HPV− OPCs, and 10 normal adult oral epithelia using a standardized global proteomic analysis platform. This analysis yielded a total of 2,653 confidently identified proteins from which we chose 31 proteins on the basis of expression differences between HPV+, HPV− and normal epithelium for targeted protein quantiation. Analysis of differentially expressed proteins by HPV status revealed enrichment of proteins involved epithelial cell development, keratinization, and extracellular matrix organization in HPV− OPC while enrichment of proteins in DNA initiation and replication and cell cycle control was found for HPV+ OPC. Enrichment analysis for transcription factor targets identified transcription factors E2F1 and E2F4 to be highly expressed in HPV+ OPC. We also found high expression of argininosuccinate synthase 1 (ASS1) in HPV+ OPC suggesting HPV+ OPC is more dependent on conditionally essential amino acid, arginine, and this was confirmed on a OPC-specific tissue microarray. These identified proteomic changes reveal novel driving molecular pathways for HPV+ and HPV− OPC that may be pertinent in therapeutic strategies and outcomes of OPC.
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影响因子：
4.4
作者：
Halvey, Patrick J.;Zhang, Bing;Coffey, Robert J.;Liebler, Daniel C.;Slebos, Robbert J. C.
通讯作者：
Slebos, Robbert J. C.
影响因子：
4.8
作者：
Fan, XL;Liu, Y;Chen, JJ
通讯作者：
Chen, JJ
DOI：
10.1016/0304-419x(93)90025-8
发表时间：
1993-05-25
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
MUNGER, K;PHELPS, WC
通讯作者：
PHELPS, WC
影响因子：
--
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
通讯作者：
Chen, Chu
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y