背景与目的 肿瘤相关长链非编码RNA(lincRNA)的异常表达影响癌症的进程,是肿瘤进展机制研究的热点,然而其调控机制目前并不清楚.本研究通过生物信息学方法研究肺腺癌lincRNA启动子DNA甲基化水平与基因表达和预后的关系.方法 从TCGA网站下载肺腺癌Illumina Methylation 450K芯片的全基因组DNA甲基化数据及转录组数据,分析DNA甲基化在lincRNA基因附近的分布情况及与基因表达的关系;比较肿瘤组织和癌旁组织DNA甲基化和表达变化.结果 lincRNA启动子附近DNA甲基化水平较低,且与基因的表达水平呈负相关.在肿瘤组织和癌旁组织间,15个lincRNA的DNA甲基化水平存在显著差异,与其表达呈反向变化,包括与癌症发生发展相关的FINDER基因,该基因启动子高甲基化的肺腺癌病人预后较差,与基因表达作用刚好相反.结论 肺腺癌中一些lincRNA启动子的DNA甲基化水平能调控lincRNA的表达,进而与肺腺癌的预后有关.%Background and objective Previous studies have found the lincRNAs play important roles in the oc-currence and development of lung adenocarcinoma, but their regulated mechanims are still unclear. The aim of this study is to evaluate the relationship between DNA methylation and lincRNA expression, and the effect of prognosis in lung adenocarci-noma. Methods The whole genome Illumina Methylation 450 DNA methylatiuon data and RNAseq for lung adenocarcinoma were download from TCGA. DNA methylation around lincRNA and their relationship to gene expression were analyzed.Their contribution to lung adenocarcinoma were further analyzed by comparing DNA methylation and lincRNA expression in tumor and adjacent tissues. Results The methylation level in promoter region was lower than other positions in lincRNA, and was negatively correlated with gene expression. There were 427 lincRNA genes showed differential DNA methylation in their promoter regions in tumor and adjacent tissues. Among these, 15 lincRNA genes showed differential gene expression and nega-tively correlated with DNA methylation, including FENDRR (a tumor progression and metastasis gene) whose high methyla-tion in its promoter showed poor survival in lung adenocarcinoma. Conclusion The expression of lincRNA can be regulated by DNA methylation in their promoter regions, and the level of DNA methylation is related to patient prognosis in lung adeno-carcinoma.
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