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

被引:19
作者
Wang, Juan [1 ,2 ,3 ]
Duan, Yong [1 ,2 ,3 ]
Meng, Qing-He [4 ]
Gong, Rong [1 ,2 ,3 ]
Guo, Chong [1 ,2 ,3 ]
Zhao, Ying [1 ,2 ,3 ]
Zhang, Yanliang [1 ,2 ,3 ]
机构
[1] Kunming Med Univ, Dept Clin Lab, Affiliated Hosp 1, Kunming, Yunnan, Peoples R China
[2] Yunnan Inst Expt Diag, Kunming, Yunnan, Peoples R China
[3] Yunnan Key Lab Lab Med, Kunming, Yunnan, Peoples R China
[4] Univ Texas MD Anderson Canc Ctr, Dept Lab Med, Houston, TX 77030 USA
来源
PLOS ONE | 2018年 / 13卷 / 10期
基金
中国国家自然科学基金;
关键词
SHOCK-PROTEIN; 20; FUNCTIONAL TUMOR-SUPPRESSOR; HEPATOCELLULAR-CARCINOMA; COLORECTAL-CANCER; AIR-POLLUTION; BETA-CATENIN; BCL6B; PATTERNS; METASTASIS; ACTIVATION;
D O I
10.1371/journal.pone.0203155
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 Xuanwei revealed several genes regulated by promoter methylation that have not been described in lung cancer before. These results provide new insight into the carcinogenesis of lung cancer in Xuanwei and represent promising new diagnostic and therapeutic targets.
引用
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页数:19
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