基于蛋白质组学的慢性阻塞性肺疾病相关肺癌的ceRNA网络构建

Construction of ceRNA network for chronic obstructive pulmonary disease related with lung cancer based on proteomics

目的拟采用蛋白质组学联合生物信息学技术构建慢性阻塞性肺疾病(COPD)相关肺癌的竞争性内源RNA(ceRNA)网络,初步探索二者的生物学机制及其潜在的核心治疗靶点。方法收集COPD相关肺癌患者及单纯肺癌患者的临床标本进行蛋白质组学分析,筛选COPD相关肺癌的差异基因并构建蛋白互作网络(PPI),对上述差异基因进行富集分析。筛选COPD相关肺癌的关键基因并在基因表达汇编(GEO)数据库进行验证,最后预测差异表达蛋白的微小RNA(miRNA)、长链非编码RNA(lncRNA),构建基于COPD相关肺癌的ceRNA网络。结果蛋白质组学分析结果显示,筛选的差异分子包括下调差异表达蛋白211个,上调差异表达蛋白168个,共计获得379个差异分子并构建PPI,进一步进行功能富集分析。在GEO数据库中检索COPD相关的芯片,结果显示GSE103174数据集共筛选了929个差异基因。检索肺癌相关芯片,GSE43346数据集共获得13605个肺癌相关差异基因。将上述结果进一步与前期蛋白质组学分析结果取交集,最终共获得2个COPD相关肺癌基因,具体为OASL、ROGDI。进一步在GEO数据集中对上述结果进行验证,并采用受试者工作特征曲线分析OASL、ROGDI在肺癌及COPD中的诊断价值,结果显示曲线下面积分别为0.784、0.731、0.688、0.785,差异均有统计学意义(P<0.05)。构建了COPD相关肺癌的lncRNA-miRNA-基因相关ceRNA网络。结论OASL和ROGDI可能成为用于COPD相关肺癌的诊断和治疗的重要生物标志物。此外,构建的ceRNA网络为进一步研究该病提供了新的方向。

Objective To construct the competitive endogenous RNA(ceRNA)network of chronic obstructive pulmonary disease(COPD)related lung cancer by proteomics combined with bioinformatics technology,and to explore the biological mechanism and potential core therapeutic targets of the two diseases.Methods The clinical specimens of patients with COPD related lung cancer and patients with lung cancer were collected for proteomics analysis.The differentially expressed genes in COPD related lung cancer were screened and the protein interaction network(PPI)was constructed,and the above differentially expressed genes were enriched.The key genes of COPD related lung cancer were screened and verified in the gene expression omnibus(GEO)database.Finally,the microRNA(miRNA)and long non-coding RNA(lncRNA)of differential proteins were predicted to construct the ceRNA network based on COPD related lung cancer.Results The results of proteomics analysis showed that 211 differentially expressed proteins were down-regulated and 168 differentially expressed proteins were up-regulated.A total of 379 differentially expressed proteins were obtained and used to construct PPI.The COPD related microarray was searched in GEO database,and the results showed that a total of 929 differentially expressed genes were screened in GSE103174 dataset.A total of 13605 lung cancer related differentially expressed genes were obtained from GSE43346 dataset.Two COPD related lung cancer genes,OASL and ROGDI,were obtained by intersection of the above results with the previous proteomics analysis results.The receiver operating characteristic curve was used to analyze the diagnostic value of OASL and ROGDI in lung cancer and COPD.The results showed that the area under the curve was 0.784,0.731,0.688 and 0.785,respectively,and the differences were statistically significant(P<0.05).The lncRNA-miRNA-gene related ceRNA network of COPD-lung cancer was constructed.Conclusion OASL and ROGDI may be used as important biomarkers for the diagnosis and treatment of COPD-related lung cancer.In addition,the constructed ceRNA network provides a new direction for further research on this disease.