Sok John C, Kuriakose M Abraham, Mahajan Vinit B, Pearlman Aaron N, DeLacure Mark D, Chen Fang-An
Division of Head and Neck Surgery and Oncology, Department of Otolaryngology, New York University School of Medicine, New York, NY 10016, USA.
Arch Otolaryngol Head Neck Surg. 2003 Jul;129(7):760-70. doi: 10.1001/archotol.129.7.760.
To identify distinct gene expression profiles of human head and neck squamous cell carcinomas (HNSCCAs) using complementary DNA (cDNA) microarray analysis and to create a preliminary, comprehensive database of HNSCCA gene expression.
Nine patients with histologically confirmed HNSCCAs, staged according to the American Joint Committee on Cancer, were enrolled. The HNSCCA tumor tissue and normal mucosal tissue were harvested at the time of surgery. A cDNA library was constructed from the paired fresh-frozen human surgical specimens of HNSCCAs and nonmalignant epithelial tissues. Biotinylated RNA was transcribed from the cDNA library and hybridized to high-density microarrays containing approximately 12 000 human genes. Altered gene expression of HNSCCAs was identified by comparison to corresponding normal mucosal tissues after a bayesian statistical analysis of variance. Results were analyzed using the gene database of the National Institutes of Health. Hierarchical clustering of the genomic data sets was determined by similarity metrics based on Pearson correlation.
Hierarchical clustering analysis revealed that the gene expression profiles obtained from the nonselected panel of 12 000 genes could distinguish the tumors from nonmalignant tissues. Gene expression changes were reproducibly observed in 227 genes representing previously identified chemokines, tumor suppressors, differentiation markers, matrix molecules, membrane receptors, and transcription factors that correlated with neoplasia, including 46 previously uncharacterized genes. Moreover, significant expression of the collagen type XI alpha1 gene and a novel gene was reproducibly observed in all 9 tumors, whereas these genes were virtually undetectable in their corresponding, adjacent nonmalignant tissues.
Complementary DNA microarray analysis of human HNSCCAs has produced a preliminary, comprehensive database of tumor-specific gene expression profiles and provided important insights into modeling gene expression changes implicated in carcinogenesis. A large-scale analysis of gene expression carries the future potential of identifying sensitive molecular markers for early tumor detection, prognosis, and novel targets for interceptive therapeutics.
利用互补脱氧核糖核酸（cDNA）微阵列分析确定人类头颈部鳞状细胞癌（HNSCCAs）不同的基因表达谱，并创建一个HNSCCA基因表达的初步综合数据库。
招募了9例经组织学确诊的HNSCCAs患者，根据美国癌症联合委员会进行分期。在手术时采集HNSCCA肿瘤组织和正常黏膜组织。从配对的新鲜冷冻的人类HNSCCAs手术标本和非恶性上皮组织构建cDNA文库。从cDNA文库转录生物素化RNA，并与包含约12000个人类基因的高密度微阵列杂交。在对贝叶斯方差进行统计分析后，通过与相应正常黏膜组织比较来确定HNSCCAs中改变的基因表达。使用美国国立卫生研究院的基因数据库分析结果。基于Pearson相关性的相似性度量确定基因组数据集的层次聚类。
层次聚类分析显示，从12000个基因的非选择面板获得的基因表达谱可以区分肿瘤组织和非恶性组织。在227个基因中可重复观察到基因表达变化，这些基因代表先前确定的趋化因子、肿瘤抑制因子、分化标志物、基质分子、膜受体和与肿瘤形成相关的转录因子，其中包括46个先前未表征的基因。此外，在所有9个肿瘤中均可重复观察到XI型胶原α1基因和一个新基因的显著表达，而在其相应的相邻非恶性组织中几乎检测不到这些基因。
对人类HNSCCAs的cDNA微阵列分析产生了一个初步的、全面的肿瘤特异性基因表达谱数据库，并为模拟致癌过程中涉及的基因表达变化提供了重要见解。基因表达的大规模分析具有识别早期肿瘤检测、预后的敏感分子标志物以及拦截性治疗新靶点的未来潜力。
