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| Genome-Wide Smoke Related Methylation Signature Genes Identification for Lung Adenocarcinomas |
| Wang Shixiang1, Zhang Fei1, Wang Ling2, Song Kai1, 3* |
1(School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China)
2(First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning, China)
3(University of Texas Southwestern Medical Center, Dallas 75235, USA) |
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Abstract To understand the biological mechanism of never smoker lung adenocarcinomas, we focused on the genome-wide methylation values (ME) to discover signature genes for the distinguishing of current/never smokers. In order to overcome the disadvantages of small-size-high-dimension, high noise and to overcome the predominate influence of the whole genome to the dozens of signature genes, a new integrative selection method was used iteratively to uncover the real signature genes. To do this, instead of using only one criteria for gene selection, we identified genes according to their significance test performance, the relationship between their methylation levels and expression levels, the biological function and the contribution to the current/never smoker classification. As a result, 48 genes were identified as ME smoke related signature genes based on the 127 lung adenocarcinoma samples downloaded from TCGA database. Then we used 64 EDRN lung adenocarcinoma samples as an independent validation set. Only using the methylation values of these 48 signature genes, the current/never smoker classification accuracy of TCGA training set is87.5% (SN=87.2%, SP=87.8%) and for EDRN validation set is 76.4% (SN=80.2%, SP=73.6%), respectively. Cross-study proved the highly cancer related of 17 important genes in our 48 signature genes. Addition to these results, we proved the importance of their corresponding methylation values. The ingenuity pathway (IPA) and Kyoto encyclopedia of genes and genomes (KEGG) pathways analysis indicated the relationships among these genes on the genetic network level and pathway levels. They also indicated they are involved in the highly cancer-related pathways.
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Received: 12 October 2015
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