Koehn Jadranka, Krapfenbauer Kurt, Huber Susanna, Stein Elisabeth, Sutter Walter, Watzinger Franz, Erovic Boban M, Thurnher Dietmar, Schindler Thomas, Fountoulakis Michael, Turhani Dritan
Department of Cranio-Maxillofacial and Oral Surgery, Medical University of Vienna, Vienna, Austria.
J Proteome Res. 2008 Sep;7(9):3818-29. doi: 10.1021/pr800077a. Epub 2008 Aug 14.
Oral squamous cellular carcinoma is a malignant tumor with poor prognosis. Discovery of early markers to discriminate between malignant and normal cells is of high importance in clinical diagnosis. Subcellular fractions from 10 oral squamous cell carcinoma and corresponding control samples, enriched in mitochondrial and cytosolic proteins, as well as blood from the tumor were analyzed by proteomics, two-dimensional gel electrophoresis, followed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Three-hundred and fifty different gene products were identified. Twenty proteins showed deranged levels in oral squamous cell carcinoma in comparison with the control samples and are potentially involved in tumor growth and metastasis. Of these, 16 proteins were upregulated. By applying pathway analysis, we found 8 of the upregulated gene products to be linked to three main locus genes, p53, MYC, and MYCN, and could be candidate biomarkers for OSCC. The findings of this pilot study show that OSCC gene ontology combined with proteomic analysis is a powerful tool in systems biology for the elucidation of the complexity of expression profiles in cellular processes. Application of such pathway analysis has the potential to generate new insights into complex molecular mechanisms underlying disease related processes and could therefore significantly contribute to the efficient performance of the entire discovery process.
口腔鳞状细胞癌是一种预后较差的恶性肿瘤。发现早期标志物以区分恶性细胞和正常细胞在临床诊断中具有重要意义。通过蛋白质组学、二维凝胶电泳，随后进行基质辅助激光解吸电离飞行时间质谱分析，对来自10例口腔鳞状细胞癌及其相应对照样本的亚细胞组分（富含线粒体和胞质蛋白）以及肿瘤血液进行了分析。共鉴定出350种不同的基因产物。与对照样本相比，有20种蛋白质在口腔鳞状细胞癌中水平紊乱，可能参与肿瘤生长和转移。其中，16种蛋白质上调。通过通路分析，我们发现8种上调的基因产物与三个主要位点基因p53、MYC和MYCN相关，可能是口腔鳞状细胞癌的候选生物标志物。这项初步研究的结果表明，口腔鳞状细胞癌基因本体论与蛋白质组学分析相结合是系统生物学中阐明细胞过程中表达谱复杂性的有力工具。这种通路分析的应用有可能为疾病相关过程背后的复杂分子机制带来新的见解，因此可以显著促进整个发现过程的高效进行。
