Integrated analysis of DNA methylation profiling and gene expression profiling identifies novel markers in lung cancer in Xuanwei, China

作者：Juan Wang, Yong Duan, Qinghe Meng, Rong Gong, Chong Guo, Ying Zhao, Yanliang Zhang · 发表于：PLoS ONE · 年份：2018 · DOI：10.1371/journal.pone.0203155 · 被引用次数：30 · 研究领域：Epigenetics and DNA Methylation、Lung Cancer Treatments and Mutations、Kruppel-like factors research

BACKGROUND: Aberrant DNA methylation occurs frequently in cancer. The aim of this study was to identify novel methylation markers in lung cancer in Xuanwei, China, through integrated genome-wide DNA methylation and gene expression studies. METHODS: Differentially methylated regions (DMRs) and differentially expressed genes (DEGs) were detected on 10 paired lung cancer tissues and noncancerous lung tissues by methylated DNA immunoprecipitation combined with microarray (MeDIP-chip) and gene expression microarray analyses, respectively. Integrated analysis of DMRs and DEGs was performed to screen out candidate methylation-related genes. Both methylation and expression changes of the candidate genes were further validated and analyzed. RESULTS: Compared with normal lung tissues, lung cancer tissues expressed a total of 6,899 DMRs, including 5,788 hypermethylated regions and 1,111 hypomethylated regions. Integrated analysis of DMRs and DEGs identified 45 tumor-specific candidate genes: 38 genes whose DMRs were hypermethylated and expression was downregulated, and 7 genes whose DMRs were hypomethylated and expression was upregulated. The methylation and expression validation results identified 4 candidate genes (STXBP6, BCL6B, FZD10, and HSPB6) that were significantly hypermethylated and downregulated in most of the tumor tissues compared with the noncancerous lung tissues. CONCLUSIONS: This integrated analysis of genome-wide DNA methylation and gene expression in lung cancer in Xu...