AUTHOR=Yu Enming , Zhang Mingshu , Xu Gongping , Liu Xiaoqi , Yan Jinglong 

TITLE=Consensus cluster analysis of apoptosis-related genes in patients with osteoarthritis and their correlation with immune cell infiltration

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1202758

DOI=10.3389/fimmu.2023.1202758

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>Osteoarthritis (OA) progression involves multiple factors, including cartilage erosion as the basic pathological mechanism of degeneration, and is closely related to chondrocyte apoptosis. To analyze the correlation between apoptosis and OA development, we selected apoptosis genes from the differentially expressed genes (DEGs) between OA and normal samples from the Gene Expression Omnibus (GEO) database, used lasso regression analysis to identify characteristic genes, and performed consensus cluster analysis to further explore the pathogenesis of this disease.</p></sec><sec><title>Methods</title><p>The Gene expression profile datasets of OA samples, GSE12021 and GSE55235, were downloaded from GEO. The datasets were combined and analyzed for DEGs. Apoptosis-related genes (ARGs) were collected from the GeneCards database and intersected with DEGs for apoptosis-related DEGs (ARDEGs). Least absolute shrinkage and selection operator (LASSO) regression analysis was performed to obtain characteristic genes, and a nomogram was constructed based on these genes. A consensus cluster analysis was performed to divide the patients into clusters. The immune characteristics, functional enrichment, and immune infiltration statuses of the clusters were compared. In addition, a protein–protein interaction network of mRNA drugs, mRNA-transcription factors (TFs), and mRNA-miRNAs was constructed.</p></sec><sec><title>Results</title><p>A total of 95 DEGs were identified, of which 47 were upregulated and 48 were downregulated, and 31 hub genes were selected as ARDEGs. LASSO regression analysis revealed nine characteristic genes: growth differentiation factor 15 (<italic>GDF15)</italic>, <italic>NAMPT</italic>, <italic>TLR7</italic>, <italic>CXCL2</italic>, <italic>KLF2</italic>, <italic>REV3L</italic>, <italic>KLF9</italic>, <italic>THBD</italic>, and <italic>MTHFD2</italic>. Clusters A and B were identified, and <italic>neutrophil activation</italic> and <italic>neutrophil activation involved in the immune response</italic> were highly enriched in Cluster B, whereas <italic>protein repair</italic> and p<italic>urine salvage</italic> signal pathways were enriched in Cluster A. The number of activated natural killer cells in Cluster B was significantly higher than that in Cluster A. <italic>GDF15</italic> and <italic>KLF9</italic> interacted with 193 and 32 TFs, respectively, and <italic>CXCL2</italic> and <italic>REV3L</italic> interacted with 48 and 82 miRNAs, respectively.</p></sec><sec><title>Conclusion</title><p>ARGs could predict the occurrence of OA and may be related to different degrees of OA progression.</p></sec>