Roblick Uwe J, Bader Franz G, Hammarstedt Lalle, Habermann Jens K, Hellman Ulf, Becker Susanne, Sundmacker Axel, Gemoll Timo, Zimmermann Kaja, Auer Gert, Munck-Wikland Eva
Department of Surgery and Laboratory for Surgical Research, University of Schleswig-Holstein, Luebeck, Germany.
Acta Oncol. 2008;47(8):1493-501. doi: 10.1080/02841860802314696.
Head and neck cancer continues to be one of the most common tumor entities worldwide. Within this group of malignancies, tonsillar squamous cell carcinoma represent approximately 15-20% of all intraoral and oropharyngeal carcinomas in the United States. Accurate and early stage diagnosis still remains a major challenge, as patients are often presented at an advanced stage of disease, causing a low overall survival rate. Thus, new diagnostic markers are highly desirable and could allow for a more reliable diagnosis, with further insights into carcinogenesis and tumor biology. Furthermore, these markers could be the basis for new therapeutic targets and early disease detection. To address these issues, we decided to use a global proteomic approach to characterize tonsillar squamous cell carcinoma.
A total of 19 tonsillar carcinoma samples and 12 benign controls acquired from the corresponding normal epithelium were analyzed by 2-D gel electrophoresis. 2-DE gels were silver stained and analyzed using the PDQuest analysis software (BioRad). Tumor specific spots were detected and identified by consecutive MALDI-TOF-MS or MS/MS polypeptide identification.
In total, 70 proteins showed significant quantitative differences in protein expression, with 50 polypeptides accessible for identification. Of those 50 polypeptides, we were able to identify a total of 27 proteins and protein isoforms, significantly up- or down-regulated in tonsillar cancer samples. In addition to previously reported polypeptides in head and neck cancers, we were able to identify several new potential marker proteins in this study.
Our results show that a combination of tonsillar cancer specific proteins can be used for histopathological diagnosis and may serve as a basis for discovering further biomarkers for early detection and prediction of response to treatment in the future.
头颈癌仍然是全球最常见的肿瘤类型之一。在这组恶性肿瘤中，扁桃体鳞状细胞癌约占美国所有口腔和口咽癌的15 - 20%。准确的早期诊断仍然是一项重大挑战，因为患者常常在疾病晚期才就诊，导致总体生存率较低。因此，非常需要新的诊断标志物，这有助于实现更可靠的诊断，并能进一步深入了解肿瘤发生和肿瘤生物学。此外，这些标志物可以成为新的治疗靶点和早期疾病检测的基础。为了解决这些问题，我们决定采用全球蛋白质组学方法来表征扁桃体鳞状细胞癌。
通过二维凝胶电泳分析了从相应正常上皮组织获取的19个扁桃体癌样本和12个良性对照样本。二维凝胶经银染后，使用PDQuest分析软件（伯乐公司）进行分析。通过连续的基质辅助激光解吸电离飞行时间质谱（MALDI - TOF - MS）或串联质谱（MS/MS）多肽鉴定来检测和识别肿瘤特异性斑点。
总共70种蛋白质在蛋白质表达上显示出显著的定量差异，其中50种多肽可用于鉴定。在这50种多肽中，我们总共能够鉴定出27种在扁桃体癌样本中显著上调或下调的蛋白质和蛋白质异构体。除了先前报道的头颈癌中的多肽外，我们在本研究中还能够鉴定出几种新的潜在标志物蛋白。
我们的结果表明，扁桃体癌特异性蛋白质的组合可用于组织病理学诊断，并可能为未来发现用于早期检测和预测治疗反应的进一步生物标志物奠定基础。
