Screening and Validation of Key Genes Associated with Non-alcoholic Fatty Liver Disease and Chronic Obstructive Pulmonary Disease

Abstract

Background: The incidence of severe hepatic steatosis is notably elevated in individuals afflicted with chronic obstructive pulmonary disease (COPD) as opposed to individuals among the general public. Many individuals with non-alcoholic fatty liver disease (NAFLD) exhibit elevated blood glucose and lipid levels, alongside an elevated Body Mass Index (BMI). These are all recognized risk factors for COPD. Objectives: This study aimed to identify shared key genes and biological pathways between NAFLD and COPD, given their common risk factors. We hypothesized these shared risk factors might indicate overlapping molecular mechanisms and sought to determine if common genetic and pathway dysregulation could explain the epidemiological link between the two diseases. Methods: A cross-sectional study design was employed. Gene expression datasets GSE63067 (NAFLD) and GSE37768 (COPD) were obtained from GEO. Differentially expressed genes (DEGs) were identified and analyzed for commonality. Protein-protein interaction networks were constructed, and GO/KEGG enrichment analyses were performed. The diagnostic value of key genes was assessed using SPSS. HepG2 cells were exposed to 1 mmol/L free fatty acids (FFAs) for 24 hours to establish the NAFLD model. The COPD model used A549 cells, which were treated with 2.5 mL of 2.5% cigarette smoke extract (CSE). Respectively, key gene protein expression was validated by Western blotting. Results: Thirty-four common genes, 41 GO items, and 10 KEGG pathways were obtained in NAFLD and COPD. Cycle protein-dependent kinase inhibitor 1A (CDKN1A), formyl peptide receptor 1 (FPR1), ficolin-1 (FCN1), and CLEC4D were identified as key genes through protein PPI network analysis. Western blot analysis revealed a notable elevation in protein levels of CDKN1A, FPR1, FCN1, and CLEC4D when compared to the control group, with statistical significance (P < 0.05). Conclusions: These key genes, preliminarily validated through cellular experiments, play a key role in the pathogenesis of NAFLD and COPD, thereby providing a novel theoretical framework for understanding the pathogenesis of these diseases.