Severino Patricia, Alvares Adriana M, Michaluart Pedro, Okamoto Oswaldo K, Nunes Fabio D, Moreira-Filho Carlos A, Tajara Eloiza H
Centro de Pesquisa Experimental, Instituto Israelita de Ensino e Pesquisa Albert Einstein, São Paulo, SP, Brazil.
BMC Res Notes. 2008 Nov 13;1:113. doi: 10.1186/1756-0500-1-113.
Oral squamous cell carcinoma (OSCC) is a frequent neoplasm, which is usually aggressive and has unpredictable biological behavior and unfavorable prognosis. The comprehension of the molecular basis of this variability should lead to the development of targeted therapies as well as to improvements in specificity and sensitivity of diagnosis.
Samples of primary OSCCs and their corresponding surgical margins were obtained from male patients during surgery and their gene expression profiles were screened using whole-genome microarray technology. Hierarchical clustering and Principal Components Analysis were used for data visualization and One-way Analysis of Variance was used to identify differentially expressed genes. Samples clustered mostly according to disease subsite, suggesting molecular heterogeneity within tumor stages. In order to corroborate our results, two publicly available datasets of microarray experiments were assessed. We found significant molecular differences between OSCC anatomic subsites concerning groups of genes presently or potentially important for drug development, including mRNA processing, cytoskeleton organization and biogenesis, metabolic process, cell cycle and apoptosis.
Our results corroborate literature data on molecular heterogeneity of OSCCs. Differences between disease subsites and among samples belonging to the same TNM class highlight the importance of gene expression-based classification and challenge the development of targeted therapies.
口腔鳞状细胞癌(OSCC)是一种常见的肿瘤,通常具有侵袭性,生物学行为不可预测且预后不良。对这种变异性分子基础的理解应能推动靶向治疗的发展,并提高诊断的特异性和敏感性。
在手术过程中从男性患者获取原发性OSCC样本及其相应手术切缘,采用全基因组微阵列技术筛选其基因表达谱。采用层次聚类和主成分分析进行数据可视化,采用单因素方差分析鉴定差异表达基因。样本大多根据疾病亚部位聚类,提示肿瘤分期内存在分子异质性。为了证实我们的结果,评估了两个公开可用的微阵列实验数据集。我们发现,在OSCC解剖亚部位之间,在目前或可能对药物开发重要的基因组方面存在显著分子差异,包括mRNA加工、细胞骨架组织与生物合成、代谢过程、细胞周期和凋亡。
我们的结果证实了关于OSCC分子异质性的文献数据。疾病亚部位之间以及属于同一TNM类别的样本之间的差异突出了基于基因表达分类的重要性,并对靶向治疗的发展提出了挑战。