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Transcriptomic and experimental identification of immune- and telomere-related genes in pelvic organ prolapse
Rong Ma1, Jingde Wu2, Jingwei Gong3
1Department of Urology, Gansu Provincial Hospital, Lanzhou, China.
Background:
Pelvic organ prolapse (POP) is a prevalent disease among women, and immune cell and telomere have potential associations with the pathogenesis of POP. The identification and validation of immune cell-related genes (ICRGs) and telomere-related genes (TRGs) in POP are of great significance for elucidating its mechanisms, screening diagnostic key genes, and identifying therapeutic targets.
Methods:
In this study, first, ICRGs were obtained based on immune infiltration and WGCNA; key genes related to immune cell and telomere in POP were identified from public-database transcriptome data through differential expression analysis, machine learning, expression level analysis and ROC analysis. Subsequently, a comprehensive analysis including nomogram construction, correlation analysis, GSEA, molecular regulatory network construction, and drug prediction explored the molecular mechanisms of these key genes in POP.
Results:
We identified 864 differentially expressed genes (DEGs), including 833 upregulated and 31 downregulated genes. The intersection of DEGs, telomere-related genes (TRGs), and immune cell-related genes (ICRGs) yielded six candidate genes. Machine learning further pinpointed CCNL1 and NAMPT as key biomarkers, which were significantly upregulated in POP samples (p < 0.05) and validated by RT-qPCR. Subsequently, a comprehensive analysis revealed their diagnostic potential via a nomogram (AUC: 0.847), a strong positive correlation (r = 0.78, p < 0.001), and enrichment in pathways such as ubiquitin-mediated proteolysis (GSEA). Molecular regulatory network construction predicted interactions with 21 key nodes and 28 interactions, and drug prediction identified 14 potential therapeutic compounds. These findings provide a theoretical basis for understanding POP pathogenesis and identifying novel therapeutic targets.
Conclusion:
This study identifies CCNL1 and NAMPT as novel immune- and telomere-related biomarkers for POP. These findings provide potential targets for diagnostic development and lay a computational foundation for future therapeutic strategies, although experimental validation is required to confirm their causal roles.
