Gottschlich Stefan, Ambrosch Petra, Cordes Christian, Görögh Tibor, Schreiber Stefan, Häsler Robert
Department of Otorhinolaryngology, Head and Neck Surgery, Christian-Albrechts-University Kiel, D-24105 Kiel, Germany.
Int J Oncol. 2006 Sep;29(3):605-13.
The molecular mechanisms causing the development of squamous cell carcinomas in the head and neck region are mostly unknown. Identification of molecular changes which are involved in carcinogenesis might play a key role in improving the diagnosis, therapy and prognosis of patients with carcinomas in the head and neck. The purpose of the study was to identify transcriptional alterations of apoptosis associated genes between normal mucosa and tumor tissue. We measured the mRNA expression of 408 apoptosis associated genes by microarray-technique in normal upper aerodigestive tract mucosa (n=4), and in cancer tissue (n=8) of squamous cell carcinomas of the upper aerodigestive tract. RT-PCR was performed to confirm the microarray results. A hierarchial cluster analysis, based on 22 selected marker-genes showing a separation of the two tissue types supports the hypothesis of a specific expression pattern associated with tumor development. Additionally, we found 11 genes associated with anti-apoptotic processes to be upregulated while 12 genes associated with proapoptotic functions as well as 5 DNA-replication and chromosome cycle associated genes were found to be downregulated in the tumor tissue. Furthermore 6 of 8 genes which are known to be associated with lymphocyte activation were upregulated in tumor edge tissue. These results represent a first step for the diagnostic use of microarrays in squamous cell carcinomas of the head and neck region and might improve the understanding of the molecular mechanisms of carcinogenesis in the head and neck region.
导致头颈部鳞状细胞癌发生发展的分子机制大多尚不明确。确定参与致癌过程的分子变化可能在改善头颈部癌患者的诊断、治疗及预后方面发挥关键作用。本研究的目的是确定正常黏膜与肿瘤组织之间凋亡相关基因的转录改变。我们采用微阵列技术测量了4例正常上呼吸道消化道黏膜及8例上呼吸道消化道鳞状细胞癌癌组织中408个凋亡相关基因的mRNA表达。进行逆转录聚合酶链反应(RT-PCR)以证实微阵列结果。基于22个选定的标记基因进行的层次聚类分析显示两种组织类型分离,支持了与肿瘤发展相关的特定表达模式这一假说。此外,我们发现肿瘤组织中有11个与抗凋亡过程相关的基因上调,而12个与促凋亡功能相关的基因以及5个与DNA复制和染色体周期相关的基因下调。此外,在肿瘤边缘组织中,已知与淋巴细胞激活相关的8个基因中有6个上调。这些结果代表了微阵列在头颈部鳞状细胞癌诊断应用中的第一步,可能会增进对头颈部区域致癌分子机制的理解。