IMAMURA Masahiro Kansai Med.Univ., Faculty of Medicine, Assistant Professor, 医学部, 講師 (40268339)
SOUGAWA Mitsuharu Kansai Med.Univ., Faculty of Medicine, Assistant Professor, 医学部, 講師 (10154684)
|Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
To reveal the genes relevant for prediction of cervical cancer after radiotherapy, we carried out cDNA microarray experiments on primary cervical cancer comparing with patients in CR group and NC groups. Some of these genes had already been associated with the radiation response, such as XRCC5 which was found more in radioresistant tumors than in radiosensitive ones. Ku80 protein, which is the gene product of XRCC5, using histopathological method of formalin-fixed sections of tumor biopsies in determining tumor response to radiotherapy and survival in 89 cervical cancer patients. Ku80-negative tumors showed significantly better responses than Ku80-positive ones, comparing CR and PR/NC responses(P=0.01). In addition, overall survival was significantly better in the Ku80-negative patients as compared with those who were Ku80-positive(P=0.04).
Next, to identify a set of genes related to thermoradiosensitivity of cervical carcinoma and to establish a predictive method. We compared the expression profiles of thermoradiosensitive and thermoradio-resistant tumors obtained by punch biopsy before treatment using a cDNA microarray consisting of 23,040 human genes. We selected 35 genes on the basis of a clustering analysis, arid confirmed the validity of these genes with a cross validation test. Some of these genes were already known to be associated with appptosis(BIK,TEGT,SSI-3), hypoxia-inducible gene(HIF1A,CA12), and tumor cell invasion and metastasis(CTSL,CTSB,PLAU,CD44). We developed a "Predictive Score" system that could clearly separate the thermoradiosensitive group from the thermoradioresistant one. These results may eventually lead to the achievement of "personalized therapy" for this disease.