| Project/Area Number |
18591540
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Chiba University |
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Principal Investigator |
SUZUKI Makoto Chiba University, Graduate School of Medicine, Assistant professor (80312940)
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| Co-Investigator(Kenkyū-buntansha) |
SHIBUYA Kiyoshi Chiba University, Chiba University Hospital, Associate professor (20302565)
SEKINE Yasuo Chiba University, Graduate Schcol of Medicine, Associate professor (70312957)
IYODA Akira Chiba University, Chiba University Hospital, Assistant Professor (10302548)
YASUFUKU Kazuhiro Chiba University, Chiba University Hospital, Assistant professor (60372356)
NAKAJIMA Takahiro Chiba University, Chiba University Hospital, Graduate student (20400913)
藤澤 武彦 千葉大学, 大学院医学研究院, 教授 (80110328)
飯笹 俊彦 千葉県がんセンター, 呼吸器科, 主任医長 (10272303)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Lung cancer / Microarray / Aberrant methylation / Mutation |
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| Research Abstract |
This study was performed for the purpose of clarifying prognostic factor and chemosensitivity in the lung cancer by gene expression profile analysis, aberrant methylation analysis, and mutation analysis. At first we performed gene expression profiling of 238 resected lung cancer cases using cDNA chip consisting of 11,000 genes which was developed originally in Chiba cancer center. Provided data was used as various genetic screening. Next we examined the following using the samples of 238 resected lung cancer cases in Chiba University Hospital. Methylation analyses were performed for IL-12Rβ2 gene which is one of subunit of the Interleukin-12 receptor, CXCL12 gene which is important for the metastasis formation, and Wnt antagonist genes (sFRP-1, sFRP-2, sFRP-5, Wif-1, Dkk-3) that are important for proliferation and growth. In addition, protein expression of both CXCR4 and β-catenin were examined. Finally, mutation analyses of EGFR and KRAS genes were performed. As a result, aberrant methylation of IL-12Rβ2 gene was common in lung cancer, and was a prognostic factor in adenocarcinomas. Aberrant methylation of CXCL12 was also common and was a prognostic factor in NSCLC. CXCL12 methylation as well as CXCR4 overexpression in tumor cells of primary site was considered to be important for the metastasis formation and the analysis of CXCL12 may become a useful prognostic marker. In addition, dysregulation of both Wnt and EGFR signaling pathways were common in NSCLC, and cross-talk between Wnt and EGFR has been identified in this study. The results may help foster development of chemotherapeutic treatments in NSCLC.
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