Identification of novel candidate genes involved in the progression of emphysema by bioinformatic methods
Identification of novel candidate genes involved in the progression of emphysema by bioinformatic methods
复制标题
通过生物信息方法鉴定参与肺气肿进展的新候选基因
DOI：
10.2147/copd.s183100
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发表时间：
2018-01-01
影响因子：
2.8
通讯作者：
Zhang, Jing
中科院分区：
文献类型：
--
作者：
Hu, Wei-Ping;Zeng, Ying-Ying;Zhang, Jing
目的通过利用生物信息学方法对基因表达总库中的GSE76925基因表达谱进行重新分析，试图寻找促进COPD患者肺气肿发生的新的候选基因。患者和方法根据GSE76925中的定量CT数据，将患者分为轻度肺气肿组(%LAA-950)和重度肺气肿组(%LAA-950)。使用Agilent GeneSpring GX v11.5(校正的P值和|折叠变化|>；1.3)鉴定差异表达基因(Deg)。通过文献挖掘和数据库检索获得已知的COPD驱动基因。STRING.org构建了DEG和已知驱动基因的蛋白质-蛋白质直接相互作用网络(PPI)，以筛选与驱动基因直接相互作用的DEG。此外，我们利用STRING.org获得了与DEGS产物相互作用的第一层蛋白，并构建了这些相互作用蛋白的间接PPI。通过将间接的PPI与驱动基因的PPI合并，我们试图发现促进肺气肿发展的潜在途径。结果所有患者均为COPD伴严重气流受限(年龄62±8岁，FEV1%=28±12岁)。共鉴定出57个degs(包括12个假基因)和135个已知驱动基因。直接PPI分析表明，GPR65、GNB4、P2RY13、NPSR1、BCR、BAG4和IMPDH2是潜在的致病基因。GPR65可调节免疫细胞对酸性微环境的反应，嗜酸性粒细胞上NPSR1‘S的表达与哮喘病情严重程度及免疫球蛋白E水平有关。间接融合PPI结果显示，TP53、IL8、CCR2、HSPA1a、Elane、PIK3CA的相互作用网络与肺气肿的发生有关。IL8、Elane和PIK3CA是参与肺气肿发病机制的分子，这也证明了TP53在肺气肿中的作用。结论GPR65、NPSR1、TP53等候选基因可能参与了肺气肿的发生发展。
Purpose By reanalyzing the gene expression profile GSE76925 in the Gene Expression Omnibus database using bioinformatic methods, we attempted to identify novel candidate genes promoting the development of emphysema in patients with COPD. Patients and methods According to the Quantitative CT data in GSE76925, patients were divided into mild emphysema group (%LAA-950<20%, n=12) and severe emphysema group (%LAA-950>50%, n=11). Differentially expressed genes (DEGs) were identified using Agilent GeneSpring GX v11.5 (corrected P-value <0.05 and |Fold Change|>1.3). Known driver genes of COPD were acquired by mining literatures and retrieving databases. Direct protein–protein interaction network (PPi) of DEGs and known driver genes was constructed by STRING.org to screen the DEGs directly interacting with driver genes. In addition, we used STRING.org to obtain the first-layer proteins interacting with DEGs’ products and constructed the indirect PPi of these interaction proteins. By merging the indirect PPi with driver genes’ PPi using Cytoscape v3.6.1, we attempted to discover potential pathways promoting emphysema’s development. Results All the patients had COPD with severe airflow limitation (age=62±8, FEV1%=28±12). A total of 57 DEGs (including 12 pseudogenes) and 135 known driving genes were identified. Direct PPi suggested that GPR65, GNB4, P2RY13, NPSR1, BCR, BAG4, and IMPDH2 were potential pathogenic genes. GPR65 could regulate the response of immune cells to the acidic microenvironment, and NPSR1’s expression on eosinophils was associated with asthma’s severity and IgE level. Indirect merging PPi demonstrated that the interacting network of TP53, IL8, CCR2, HSPA1A, ELANE, PIK3CA was associated with the development of emphysema. IL8, ELANE, and PIK3CA were molecules involved in the pathological mechanisms of emphysema, which also in return proved the role of TP53 in emphysema. Conclusion Candidate genes such as GPR65, NPSR1, and TP53 may be involved in the progression of emphysema.