肺炎衣原体阳性的非小细胞肺癌患者全基因组 DNA甲基化与lncRNA-mRNA表达分析

Genome-wide analysis on non-small cell lung cancer with chlamydia pneumoniae positive patients of DNA methylation and expression of lncRNA-mRNA

目的基于肺炎衣原体感染(Cpn)的非小细胞肺癌患者全基因组DNA甲基化与lncRNA-mRNA的表达情况分析,探索肺癌生物标志物。方法收集6对Cpn感染非小细胞肺癌患者的癌与癌旁组织,进行全基因组DNA甲基化芯片、lncRNA/mRNA芯片分析,筛选差异甲基化基因、差异表达的lncRNA及mRNA,将3者联合分析并进行GO分析及KEGG通路分析。结果共筛选出3940个差异表达lncRNA,5105个差异表达mRNA;得到11306对lncRNA-mRNA共表达对。发现了115个差异甲基化基因,含24个DNA甲基化-mRNA关联对。最终筛选35个lncRNA/DNA甲基化-mRNA关联对,包含6个差异基因,即ZIK1、FAM184、CHRN、CPLX、NAV2和SCUBE2。GO分析及KEGG通路分析发现筛选的差异基因功能与信号通路与肿瘤发生有关。结论DNA甲基化与lncRNA共同调控mRNA表达状态,影响ZIK1、FAM184、CHRN、CPLX、NAV2和SCUBE2等基因的功能,进一步影响Cpn感染的非小细胞肺癌的发生发展。

Objective To explore biomarkers of chlamydia pneumoniae(Cpn)positive non-small cell lung cancer,with genome-wide DNA methylation and lncRNA-mRNA expression analysis.Methods Six pairs of tumor and non-tumor adjacent tissues of Cpn non-small cell lung cancer were conducted to genome-wide DNA methylation chip and lncRNA-mRNA chip analysis.LncRNA-mRNA co-expression pairs and DNA methylation-mRNA association pairs were constructed to further combined analysis,and GO analysis and KEGG pathway analysis were performed on selecting differentially expressed genes.Results Totally 3940 differential lncRNAs and 5105 differentially expressed mRNAs were screened out.Totally 11306 pairs of lncRNA-mRNA co-expression pairs were obtained,and 115 differential methylated genes were found by combined analysis,including 24 DNA methylation-mRNA association pairs.Finally,totally 35 lncRNA/DNA methylation-mRNA pairs were found by combined analysis,including six differentially expressed genes(ZIK1,FAM184B,CHRNE,CPLX2,NAV2,SCUBE2).The functions and signaling pathways of differentially expressed genes were related to tumorigenesis by using GO analysis and KEGG pathway analysis.Conclusion DNA methylation and lncRNA co-regulating the expression status of mRNA,will affect the functions of ZIK1,FAM184,CHRN,CPLX,NAV2 and SCUBE2,and further affect the occurrence and development of pneumoniae positive non-small cell lung cancer.