Shared Biomarkers and Pathways in Psoriasis and Cervical Squamous Cell Carcinoma
According to a study published in Frontiers in Immunology, psoriasis may be linked to an increased risk of cervical squamous cell carcinoma (CESC) through shared systemic inflammatory pathways. This study aimed to uncover the key genes, pathways, and immune cells connecting psoriasis and CESC.
Researchers utilized the GSE63514 CESC dataset from the Gene Expression Omnibus and combined 2 psoriasis datasets (GSE13355 and GSE14905) into a single comprehensive dataset after adjusting for batch effects. Differentially expressed genes were identified using Limma and co-expression network analysis. A random forest (RF) machine learning algorithm was employed to pinpoint hub genes. Gene enrichment pathways were analyzed via gene ontology and the KEGG pathway, while immune cell infiltration in psoriasis and CESC samples was assessed using CIBERSORT. The study also constructed miRNA-mRNA and transcription factor-mRNA regulatory networks using Cytoscape, identified potential drug targets from the cMAP database, and quantified biomarker expression in HeLa and psoriatic cell models using reverse transcription-quantitative polymerase chain reaction.
The analysis revealed 27 key genes associated with both psoriasis and CESC, with NCAPH, UHRF1, CDCA2, CENPN, and MELK identified as hub genes through RF. Enrichment pathways highlighted chromosome segregation, nucleotide binding, and DNA methylation during the mitotic cell cycle as significant. Immune cell infiltration analysis further emphasized the interplay between the immune response in psoriasis and CESC. The cMAP database identified 10 small molecule compounds targeting the central genes as potential therapeutic agents. Regulatory network analysis pinpointed 3 miRNAs and 9 transcription factors closely linked to the 5 key genes, validated through external datasets and clinical samples. Diagnostic efficacy was confirmed via receiver operating characteristic curves, and experimental validation was conducted in HeLa and psoriatic cell models.
In conclusion, the study identified 5 crucial biomarkers—NCAPH, UHRF1, CDCA2, CENPN, and MELK—highlighting their role in the shared pathogenesis of psoriasis and CESC. These findings offer new diagnostic and therapeutic insights for both conditions.
Reference
Liu L, Yin P, Yang R, et al. Integrated bioinformatics combined with machine learning to analyze shared biomarkers and pathways in psoriasis and cervical squamous cell carcinoma. Front Immunol. Published online May 28, 2024. doi:10.3389/fimmu.2024.1351908