Sticht Carsten, Freier Kolja, Knöpfle Karl, Flechtenmacher Christa, Pungs Susanne, Hofele Christof, Hahn Meinhard, Joos Stefan, Lichter Peter
Abteilung Molekulare Genetik (B060), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
Neoplasia. 2008 May;10(5):462-70. doi: 10.1593/neo.08164.
In an attempt to further elucidate the pathomechanisms in oral squamous cell carcinoma (OSCC), gene expression profiling was performed using a whole-transcriptome chip that contains 35,035 gene-specific 70 mere oligonucleotides (Human OligoSet 4.0; Operon, Cologne, Germany) to a set of 35 primary OSCCs. Altogether, 7390 genes were found differentially expressed between OSCC tumor samples and oral mucosa. To characterize the major biologic processes in this tumor collection, MAPPFinder, a component of GenMAPP version 2.1, was applied to this data set to generate a statistically ranked list of molecular signaling pathways. Among others, cancer-related pathways, such as mitogen-activated protein (MAP) kinase signaling (z score = 4.6, P < .001), transforming growth factor-beta signaling (z score = 3.0, P = .015), and signaling pathways involved in apoptosis (z score = 2.1, P = .037), were found deregulated in the OSCC collection analyzed. Focusing on the MAP kinase signaling pathway, subsequent tissue microarray analyses by immunohistochemistry revealed an increase in protein expression of MAP kinase-related proteins ERK1 in 22.8% (48 of 209) and ERK5 in 27.4% (76 of 277), respectively. An association of high ERK5 but not of high ERK1 expression with advanced tumor stage and the presence of lymph node metastases was found (P = .008 and P = .016, respectively). Our analysis demonstrates the reliability of the combined approach of gene expression profiling, signaling pathway analyses, and tissue microarray analysis to detect novel distinct molecular aberrations in OSCC.
为了进一步阐明口腔鳞状细胞癌（OSCC）的发病机制，使用包含35,035个基因特异性70聚寡核苷酸的全转录组芯片（人类寡核苷酸集4.0；德国科隆Operon公司）对35例原发性OSCC进行基因表达谱分析。总共发现7390个基因在OSCC肿瘤样本和口腔黏膜之间存在差异表达。为了表征该肿瘤样本集中的主要生物学过程，将GenMAPP 2.1版本的组件MAPPFinder应用于该数据集，以生成分子信号通路的统计排名列表。在其他方面，发现癌症相关通路，如丝裂原活化蛋白（MAP）激酶信号通路（z值=4.6，P<.001）、转化生长因子-β信号通路（z值=3.0，P=.015）以及参与细胞凋亡的信号通路（z值=2.1，P=.037）在分析的OSCC样本集中失调。聚焦于MAP激酶信号通路，随后通过免疫组织化学进行的组织微阵列分析显示，MAP激酶相关蛋白ERK1的蛋白表达在22.8%（209例中的48例）中增加，ERK5的蛋白表达在27.4%（277例中的76例）中增加。发现高ERK但不是高ERK1表达与肿瘤晚期和淋巴结转移的存在相关（分别为P=.008和P=.016）。我们的分析证明了基因表达谱分析、信号通路分析和组织微阵列分析相结合的方法在检测OSCC中新型独特分子异常方面的可靠性。
