Prediction of lung cancer prognosis, and anticancer drug sensitivity by diversified clinical-gene set screening through microarray analysis, mutation, and aberrant methylation

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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.