以蛋白質體學為基礎來尋找新的口腔癌腫瘤標記

Abstract

Oral cancer is the sixth most frequent cancer in the world. Buccal mucosa originated squamous cell carcinoma (SCC) is one of the most aggressive oral cancers. It mainly occurs in Taiwan, Central and Southeast Asia, and is closely related to the practice of tobacco smoking and betel squid chewing. The high recurrence and low survival rates of buccal SCC remained an important focus for us to understand the pathogenesis of the disease in order to design better therapeutic strategies. Here we applied novel proteomic technology to analyze oral cancer cell lines and paired N/T buccal SCC tissues to identify tumor-associated proteins as new oral cancer biomarkers or molecular targets. We further evaluated a novel cancer therapeutical compound deguelin global protein response in oral cancer cell line SAS. Our result showed a number of proteins were found to be significantly over-expressed or down-regulated in oral cancer cell lines and clinical samples. These increased proteins included glycolytic enzymes, heat-shock proteins, tumor antigens, cytoskeleton proteins, enzymes involved in detoxification and anti-oxidation systems, and proteins involved in mitochondrial and intracellular signaling pathways. These extensive protein variations indicate that multiple cellular pathways were involved in the process of tumorigenesis, and suggest that multiple protein molecules should be simultaneously targeted as an effective strategy to counter the disease. In our results, at least, we have identified Thymosin β4, ubiquitin, BUB3, in addition to several novel proteins are candidates for targeted proteins in oral cancers. Validation of Thymosin β4 protein expression in N/T paired oral cancer tissue array by immunohistochemistry analysis revealed that Thymosin β4 overexpression was found mainly in late clinical stage oral cancer samples. The thymosin β4/ILK/Akt pathway analysis also showed similar trend for the activation of this pathway in oral cancers. Altogether, the present findings also demonstrated that rich protein information can be produced by means of proteomic analysis for a better understanding of the oncogenesis and pathogenesis in a global way, which in turn is a basis for the rational designs of diagnostic and therapeutic methods in oral cancers.