2005 Fiscal Year Final Research Report Summary
Exhausitive search for the identification of lung cancer specific gene splicing by microarray technique
| Project/Area Number |
15390407
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | Tohoku University |
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Principal Investigator |
KONDO Takashi Tohoku University, Institute of Development Aging and Cancer, Professor, 加齢医学研究所, 教授 (10195901)
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| Co-Investigator(Kenkyū-buntansha) |
SAKURADA Akira Tohoku University, Hospital, Assistant Professor, 病院・助手 (60360872)
TABATA Toshiharu Tohoku University, Institute of Development Aging and Cancer, Assistant Professor, 加齢医学研究所, 助手 (40361191)
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| Project Period (FY) |
2003 – 2005
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| Keywords | small peripheral lung adenoca. / GGO / CT M / L ratio / TIMP-2 / Ki-67 / Methylation / microarray |
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| Research Abstract |
Peripheral small lung adenocarcinomas have been detected more frequently in these days according as CT screening has become popular. The computed tomographic M/L ratio (area of the tumor in the mediastinal computed tomographic image/area of the tumor in the lung computed tomographic image) of small peripheral lung adenocarcinoma is correlated with patient prognosis. The numbers of patients with high labeling indexes of Ki-67 and high expression of vascular endothelial growth factor, CD34, matrix metalloproteinase2, and matrix metalloproteinase9 in the solid-type group (computed tomographic M/L ratio >50%) are significantly higher than those in the faint density-group (computed tomographic M/L ratio <50%). The number of patients with high levels of CD44v6 or tissue inhibitor of matrix metalloproteinase2 staining in the faint density-type group is significantly higher than that in the solid-type group. Independent variables capable of predicting computed tomographic M/L ratio included CD34, matric metalloproteinase 2, matrix metalloproteinase 9, and tissue inhibitor of matrix metalloproteinase 2.
Aberrant methylation of DNA is an important event in carcinogenesis. A microarrray analysis of DNA methylation in the promoter regions of genes using a newly developed promoter-associated methylated DNA amplification DNA chip. About 10.9% of the cancer-related genes are hypermethylated in lung cancer cell lines. Notably, HIC1, IRF7, ASC, RIPK3, RASSF1A, FABP3, PRKCDBP, and PAX3 genes are hypermethylated in most lung cancer cell lines examined. The expression profiles of these genes correlated to the methylation profiles of the genes, indicating that the microarray analysis of DNA methylation in the promoter region of the genes is convenient for epigenetic study.
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