| Co-Investigator(Kenkyū-buntansha) |
HOSHINA Hideyuki Dental Hospital, Niigata University, Lecturer, 歯学部・附属病院, 講師 (30173587)
SAKU Takashi Graduate School of Medical and Dental Sciences, Niigata University, Professor, 大学院・医歯学総合研究科, 教授 (40145264)
TAKAGI Ritsuo Graduate School of Medical and Dental Sciences, Niigata University, Professor, 大学院・医歯学総合研究科, 教授 (20143795)
FUJITA Hajime Graduate School of Medical and Dental Sciences, Niigata University, Assistant, 大学院・医歯学総合研究科, 助手 (60271805)
IDA Hiroko Graduate School of Medical and Dental Sciences, Niigata University, Assistant, 大学院・医歯学総合研究科, 助手 (60293213)
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| Research Abstract |
We performed gene expression profiling with 500 of the cancer related genes to develop diagnostic system of oral squamous cell carcinoma (OSCC). To eliminate biases caused by difference between tumors or measurements, we selected increased arid decreased genes in all OSCC cases. Unchangeable decreases were observed in gene expression ratio of Retinoic acid receptor gamma, Keratin family genes, and some molecules of desmosomes components against normal oral mucosa. Regular increases were observed in extracellular matrix (ECM)-degrading enzymes such as MMPs, uPA; ECMs such as Tenascin C and Fibronectin 1; Chemokines or transcription factors, such as MIG, IP-10, STAT1, BIGH3, that were induced by growth factors. Results of a cluster analysis indicated the similarity in gene expression patterns between those genes. The expression profile of cancer related genes in OSCC tissues seemed to reflect loss of epithelial characteristics, activated tissue destruction and formation of the cancer str
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oma, and disturbed phases in signal transudation systems. Comparison between groups with or without the involvement of lymphnode metastasis revealed significantly increased expression of MMP-1, uPA, CD44, Integrin alpha 3 and Paxillin as well as decreased mRNA levels of CD9 and IGFBP2. To confirm the results of gene expression analysis, we preformed immunohistochemistry for the genes that were suggested to associate with metastatic behavior of OSCCs. MMP-1, MMP-3 and uPA were co-localized extensively in inflammatory cells, endotherial cells and ECM structure, but no localization was indicated in tumor cells. Prominent staining of those gene products were observed on eosinophilic, round shaped mononuclear cells that were associated with degrading of surrounding collagen fibers and capillary structures. These histological findings corroborate the co-regulated expression and cooperative function of those ECM-degrading enzymes that were expected in gene expression analyzes. Striking correlation was demonstrated between MMP-1 mRNA revel and lymph node metastasis (U=0, p=0.001). MMP-1 could be an independent and accurate prognostic factor of lymph node metastasis for OSCC. By identifying commonly regulated and characteristic clusters of coexpressed genes, and by compeering the gene expression data with the extensive clinical data, and then by using immunohistochemistry against a subset of significant genes, surgical specimens with diverse backgrounds can be made accessible to extract valuable genes without prior dissection into components of tumor tissue. Less
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