慢性阻塞性肺疾病中自噬相关基因的鉴定和验证。
Identification and Validation of Autophagy-Related Genes in Chronic Obstructive Pulmonary Disease.
机构信息
Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin 300052, People's Republic of China.
出版信息
Int J Chron Obstruct Pulmon Dis. 2021 Jan 12;16:67-78. doi: 10.2147/COPD.S288428. eCollection 2021.
PURPOSE
Autophagy plays essential roles in the development of COPD. We aim to identify and validate the potential autophagy-related genes of COPD through bioinformatics analysis and experiment validation.
METHODS
The mRNA expression profile dataset GSE38974 was obtained from GEO database. The potential differentially expressed autophagy-related genes of COPD were screened by R software. Then, protein-protein interactions (PPI), correlation analysis, gene-ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied for the differentially expressed autophagy-related genes. Finally, RNA expression of top five differentially expressed autophagy-related genes was validated in blood samples from COPD patients and healthy controls by qRT-PCR.
RESULTS
A total of 40 differentially expressed autophagy-related genes (14 up-regulated genes and 26 down-regulated genes) were identified between 23 COPD patients and 9 healthy controls. The PPI results demonstrated that these autophagy-related genes interacted with each other. The GO and KEGG enrichment analysis of differentially expressed autophagy-related genes indicated several enriched terms related to autophagy and mitophagy. The results of qRT-PCR showed that the expression levels of and in COPD patients and healthy controls were consistent with the bioinformatics analysis results from mRNA microarray.
CONCLUSION
We identified 40 potential autophagy-related genes of COPD through bioinformatics analysis. and may affect the development of COPD by regulating autophagy. These results may expand our understanding of COPD and might be useful in the treatment of COPD.
目的
自噬在 COPD 的发展中起着至关重要的作用。我们旨在通过生物信息学分析和实验验证，鉴定和验证 COPD 的潜在自噬相关基因。
方法
从 GEO 数据库中获取 mRNA 表达谱数据集 GSE38974。使用 R 软件筛选 COPD 的潜在差异表达自噬相关基因。然后，进行蛋白质-蛋白质相互作用（PPI）、相关性分析、基因本体论（GO）富集分析和京都基因与基因组百科全书（KEGG）通路富集分析，对差异表达的自噬相关基因进行分析。最后，通过 qRT-PCR 验证 COPD 患者和健康对照者血液中前 5 个差异表达自噬相关基因的 RNA 表达。
结果
在 23 名 COPD 患者和 9 名健康对照者之间共鉴定出 40 个差异表达的自噬相关基因（14 个上调基因和 26 个下调基因）。PPI 结果表明这些自噬相关基因相互作用。差异表达自噬相关基因的 GO 和 KEGG 富集分析表明，几个与自噬和线粒体自噬相关的富集项。qRT-PCR 结果表明，在 COPD 患者和健康对照者中，和的表达水平与 mRNA 微阵列的生物信息学分析结果一致。
结论
通过生物信息学分析，我们鉴定出 40 个 COPD 的潜在自噬相关基因。和可能通过调节自噬影响 COPD 的发生发展。这些结果可能扩展我们对 COPD 的认识，并可能有助于 COPD 的治疗。
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