Identification of Potential Hub Genes Linked to Chronic Obstructive Pulmonary Disease and Mild Cognitive Impairment Using Bioinformatic Analysis

Abstract

Background: Chronic obstructive pulmonary disease (COPD) and mild cognitive impairment (MCI) are two conditions that are closely associated with worse progression and prognosis. However, the potential common pathogenetic mechanisms and genetic modulators that link these two conditions remain elusive. This study aimed to investigate the shared differentially expressed genes (DEGs) to reveal the co-genetic features and molecular mechanisms between COPD and MCI. Methods: Overlapping DEGs were identified from the COPD dataset (GSE148004) and the MCI dataset (GSE63060). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted based on the overlapping genes to annotate the biological signaling pathways. Then, a protein-protein interaction (PPI) network was constructed using the STRING database and Cytoscape software to screen out the key subnetworks and hub genes. Finally, the hub genes were validated in external datasets (GSE11784, GSE106986, and GSE63061) to enhance the reliability and efficacy of the results. Results: In total, 26 overlapping DEGs in COPD and MCI, as well as crucial pathways such as adenosine triphosphate (ATP) synthesis coupled electron transport, respiratory electron transport chain, and oxidative phosphorylation were obtained. Through the constructed PPI network, 12 hub genes were identified, including ATP5C1, ATP5J, ATP5O, cytochrome c oxidase subunit 7C (COX7C), histidine triad nucleotide binding protein 1 (HINT1), NADH:ubiquinone oxidoreductase subunit A1 (NDUFA1), NDUFB2, NDUFA4, NDUFS4, NDUFS5, translocase of outer mitochondrial membrane 7 (TOMM7), and ubiquinol-cytochrome c reductase complex III subunit VII (UQCRQ), along with their enriched biological pathways, oxidative phosphorylation, and ATP metabolic process. The validation of hub genes in external datasets showed that ATP5C1, COX7C, NDUFA1, and NDUFS5 might be the pivotal therapeutic targets. Conclusions: To uncover the underlying mechanisms between COPD and MCI, this study identified the hub genes and corresponding regulatory mitochondrial pathways, which might provide promising insights and novel strategies for further research.