He Jie, Li Xiaoyan
Clinical Medical College of Chengdu Medical College, Chengdu, China.
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China.
Front Genet. 2022 Feb 8;13:780010. doi: 10.3389/fgene.2022.780010. eCollection 2022.
Aging plays a significant role in the occurrence and development of idiopathic pulmonary fibrosis (IPF). In this study, we aimed to identify and verify potential aging-associated genes involved in IPF using bioinformatic analysis. The mRNA expression profile dataset GSE150910 available in the Gene Expression Omnibus (GEO) database and R software were used to identify the differentially expressed aging-related genes involved in IPF. Hub gene expression was validated by other GEO datasets. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on differentially expressed aging-related genes. Subsequently, aging-related genes were further screened using three techniques (least absolute shrinkage and selection operator (LASSO) regression, support vector machine, and random forest), and the receiver operating characteristic curves were plotted based on screening results. Finally, real-time quantitative polymerase chain reaction (qRT-PCR) was performed to verify the RNA expression of the six differentially expressed aging-related genes using the blood samples of patients with IPF and healthy individuals. Sixteen differentially expressed aging-related genes were detected, of which the expression of 12 were upregulated and four were downregulated. GO and KEGG enrichment analyses indicated the presence of several enriched terms related to senescence and apoptotic mitochondrial changes. Further screening by LASSO regression, support vector machine, and random forest identified six genes ( and ) that could serve as potential diagnostic biomarkers for IPF. Furthermore, qRT-PCR analysis indicated that among the above-mentioned six aging-related genes, only the expression levels of and in patients with IPF and healthy individuals were consistent with the results of bioinformatic analysis. In conclusion, bioinformatics analysis identified 16 potential aging-related genes associated with IPF, and clinical sample validation suggested that among these, and might play a role in the incidence and prognosis of IPF. Our findings may help understand the pathogenesis of IPF.
衰老在特发性肺纤维化(IPF)的发生和发展中起重要作用。在本研究中,我们旨在通过生物信息学分析鉴定和验证参与IPF的潜在衰老相关基因。利用基因表达综合数据库(GEO)中可用的mRNA表达谱数据集GSE150910和R软件来鉴定参与IPF的差异表达衰老相关基因。通过其他GEO数据集验证枢纽基因表达。对差异表达的衰老相关基因进行基因本体(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。随后,使用三种技术(最小绝对收缩和选择算子(LASSO)回归、支持向量机和随机森林)进一步筛选衰老相关基因,并根据筛选结果绘制受试者工作特征曲线。最后,使用IPF患者和健康个体的血样进行实时定量聚合酶链反应(qRT-PCR)以验证六个差异表达的衰老相关基因的RNA表达。检测到16个差异表达的衰老相关基因,其中12个表达上调,4个表达下调。GO和KEGG富集分析表明存在几个与衰老和凋亡线粒体变化相关的富集术语。通过LASSO回归、支持向量机和随机森林进一步筛选确定了六个基因(和),它们可作为IPF的潜在诊断生物标志物。此外,qRT-PCR分析表明,在上述六个衰老相关基因中,只有IPF患者和健康个体中的和的表达水平与生物信息学分析结果一致。总之,生物信息学分析鉴定了16个与IPF相关的潜在衰老相关基因,临床样本验证表明,其中和可能在IPF的发生和预后中起作用。我们的发现可能有助于理解IPF的发病机制。