| Co-Investigator(Kenkyū-buntansha) |
TAKADA EIio Tokyo Medial University, School of Medicine, Assistant Professor (50110903)
YANASE Noriko Tokyo Medial University, School of Medicine, Instructor (10210303)
HATA Kikumi Tokyo Medial University, School of Medicine, Instructor (30287156)
CHIBA Hiroshige Tokyo Medial University, School of Medicine, Professor (80105478)
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| Research Abstract |
Oral squamous cell carcinoma (OSCC), the most common tumor in the oral cavity, has increased in number in recent years. Although conventional treatments including surgical operation, hemotherapy, and adjuvant radiotherapy, have some efficacy, 5-year survival rates have not improved significantly. Local recurrence and/or distant metastases following definitive therapy are a major cause of mortality. Identification of biomarkers that predict patients at high-risk for recurrence is a compelling need. In this project, we aimed to carry out comprehensive genome-wide assessment of gene expression to identify prognostic biomarkers for OSCC development and metastasis. First, distinct expression patterns including signal transduction, receptor activity, transcriptional regulation, and apoptosis-related genes were observed in primary and metastatic tissues Furthermore, distinct gene-expression profiles were detected in primary tumors with or without metastases. The primary tumors without metasta
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ses were further subdivided into two groups, low and intermediate. These findings might suggest that our gene expression signature(s) represent prognostic marker(s) associated with a high- or low-risk of tumor metastases. Induction of apoptosis is implicated in tumor development and/or metastasis. Bax, a member of BCL-2 family proteins, functioned as proapoptotic molecules in OSCC and was activated by c-Jun NH_2-terminal kinase (JNK). Bax protein was cleaved into a truncated form (tBax) during a late phase of apoptotic processes, probably representing an amplification of apoptotic events. In contrast, NF-kB counteracted induction of apoptosis, through upregulation of BCL-xL and/or c-FLIP. These observations suggest that the balance between proapoptotic and survival signals determines the cell fate, and therapeutic intervention of this balance may be effective for treatment of patients with tumors.
Together, further studies are required to confirm these observations in an independent, prospectively cohort studies with the goal of implementing the gene expression signature into the clinical management of patients with OSCC. Less
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