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头颈部鳞状细胞癌中的基因表达谱和生物学通路改变

Genetic expression profiles and biologic pathway alterations in head and neck squamous cell carcinoma.

作者信息

Choi Peter, Chen Chu

机构信息

Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle, 98109, USA.

出版信息

Cancer. 2005 Sep 15;104(6):1113-28. doi: 10.1002/cncr.21293.

Abstract

Head and neck squamous cell carcinoma (HNSCC) is associated with considerable mortality and morbidity and is a major public health concern worldwide. To date, > 20 studies incorporating DNA microarray analyses have examined genomewide genetic expression changes associated with the development of HNSCC. The authors identified published reports of genetic expression profiles of HNSCC by Medline database search. They performed a review of the reports to identify genes that have been found repeatedly to exhibit substantially altered expression in HNSCC. Genes with altered expression were subsequently examined in the context of defined biologic systems with the use of GenMapp 2.0 pathway analysis software. Genes most commonly found to exhibit altered expression were those encoding for cytoskeletal and extracellular matrix proteins, inflammatory mediators, proteins involved in epidermal differentiation, and cell adhesion molecules. Results of GenMapp 2.0 analysis suggested global down-regulation of genes that encode for ribosomal proteins and enzymes in the cholesterol biosynthesis pathway; and up-regulation of genes that encode for matrix metalloproteinases and genes that bear on the inflammatory response. The review indicated that there are several genes and pathways that exhibit substantially altered expression in cancerous versus noncancerous states across studies. Further investigation into the genomic, proteomic, and functional consequences of these gene expression alterations may provide insight into the pathophysiology of HNSCC.

摘要

头颈部鳞状细胞癌(HNSCC)与相当高的死亡率和发病率相关,是全球主要的公共卫生问题。迄今为止,已有超过20项纳入DNA微阵列分析的研究检测了与HNSCC发生相关的全基因组遗传表达变化。作者通过检索Medline数据库确定了已发表的HNSCC基因表达谱报告。他们对这些报告进行了综述,以确定那些在HNSCC中反复被发现表达有显著改变的基因。随后,使用GenMapp 2.0通路分析软件,在特定的生物系统背景下对表达改变的基因进行了研究。最常被发现表达改变的基因是那些编码细胞骨架和细胞外基质蛋白、炎症介质、参与表皮分化的蛋白以及细胞粘附分子的基因。GenMapp 2.0分析结果表明,编码核糖体蛋白和胆固醇生物合成途径中酶的基因整体下调;编码基质金属蛋白酶的基因以及与炎症反应相关的基因上调。该综述表明,在各项研究中,有几个基因和通路在癌组织与非癌组织状态下表达有显著改变。对这些基因表达改变的基因组学、蛋白质组学和功能后果进行进一步研究,可能有助于深入了解HNSCC的病理生理学。

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