|Budget Amount *help
¥15,270,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥870,000)
Fiscal Year 2007: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2006: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2005: ¥8,300,000 (Direct Cost: ¥8,300,000)
【Aim】 Gene expression analysis of oral squamous cell carcinoma tissues were ferformed with Integrin family genes (ITG), Tetraspanin genes (TSPAN), Cycline and CDK genes as biomarkers of the malignancy of the cancer.
【Material and method】 Total RNA were extracted from whole oral squamous carcinoma tissues, and were subjected to reversetranscription synthesis for first strand cDNAs as templates for the Mowing real-time polymerase chain reaction (RTQ-PCR) process. Real time monitoring of RTQ-PCR were done with TaqMan promes specific for each subjected gems.
69 cases of tongue squamous cell carcinoma and 73 cases of gingival squamous cell carcinoma of upper and lower jaws were used as the subject of the gene expression analysis. Integrin family genes: ITGA1, ITGA2, ITGA3, ITGA5, ITGA6, ITGAv, ITGB1, ITGB3, ITGB4, ITGB5, ITGB6, and Tetraspanin family genes; CD9, CD81,CD82,CD63,CD151, and growth factor related gene: EGFR, and cyclins / thire inhibitors: CCND1, CCND2, CDK4, CDK2, Ki67, and prot
ease genes; MMP-1, -2, -3, -4, -7, -8, -9, -10, -11, -12, -13, -14, NM23 were all subjected to analyses Expression levels of house keeping genes (GAPD, ACTB, 18sRNA), and epitherial cytoskeleton molecule gene (KRT5), and desmosomal components molecule genes (JUP, PXN) were also quantified and used for standarization of the expression level of subjected genes in the process of analyses. These gene expression ratios were subjected to the relation analyses with cervical lymph node metastasis, other clinical parameters and death outcome based on unifactorial and seriese of multifactorial statistical methods.
(1)ITGB4/JUP, ITGB5/ACTB demonstrated significant relation with the distant organ metastasis and death outcome. On the other hand, ITGA3/KRT5, ITGA3/JUP showed relation to cervical lymph node metastasis without uncontrollable consequences.
(2)CD9/ACTB, CD9/CD82, and some CD9, MMP-1 gene expression ratios demonstrated significant relation to cervical lymph node metastasis and death outcome.
(3)CCND1 showed relation to poor prognosis including cervical lymphnode metasitasis and death outcome.
(4)NM23 and EGFR didn't exhibit any significance with poor clinical outcomes.
【Discussion】 There seemed to be two types of metastatic trait in oral squamous cell carcinomas, one was ivasive phenotype within local regional metastasis and another was lymphnode metastasis with agrresive phenotype to metastatize to distant organs. These biological characteristics were effectively assesed with the expression levels of ITGA3, ITGB4 and ITGB5. Less