Exploring the Pathogenesis and Potential Therapeutic Drugs of Chronic Obstructive Pulmonary Disease Based on Functional Disorder Modules

Abstract

Researchers widely acknowledged that chronic obstructive pulmonary disease (COPD) became the third leading cause of death in the United States. At present, the pathogenesis and treatment of COPD still need to be further explored. In this study, the pathogenesis and treatment of COPD were modularized, and effective therapeutic drugs were explored. First, we identified 467 COPD-related genes from the NCBI-Gene database to explore the co-expression of these genes and their highly interacting proteins in patients with COPD. Secondly, COPD-related genes were analyzed using a co-expression module. Then, crosstalk analysis of co-expression modules was performed to reveal the interaction between these modules. Next, the enrichment of GO function and KEGG pathway module genes was analyzed. At the same time, non-coding RNAs (ncRNAs), transcription factors that regulate modules and potential drugs were predicted using hypergeometric tests. In summary, we obtained 22 co-expression modules, and a significant relationship was found between these modules. From the results of this study, we determined that the identified module genes are involved in the biological processes of cell growth, leukocyte activation, cytokine production, and humoral immune responses. Wnt, NF-kappa B, PI3 K-AKT, mitochondrial autophagy, oxidative stress, and other signaling pathways were significantly regulated. In addition, a ncRNA pivot (including microRNA-93-5p and microRNA-128-3p) and TF pivot (including NFKB1, RELA, and SP1) were identified as significant regulatory dysfunction modules. Finally, according to the target effect of drugs on the module genes, we found that drugs, such as fostamatinib and copper, demonstrate a certain therapeutic effect on COPD. In conclusion, COPD multifactorial dysfunction, in which helps to reveal the disease, at that meantime, to improve its basic molecular mechanisms. These findings provide valuable theoretical references for the diagnosis and personalized treatment of patients with COPD.