Identification of potential molecular mechanisms and therapeutic targets for recurrent pelvic organ prolapse

Quan Zhou; Man Lu; Guo-Sheng Li; Gan-Lu Peng; Yan-Feng Song

doi:10.1016/j.heliyon.2023.e19440

Identification of potential molecular mechanisms and therapeutic targets for recurrent pelvic organ prolapse

Heliyon. 2023 Aug 27;9(9):e19440. doi: 10.1016/j.heliyon.2023.e19440. eCollection 2023 Sep.

Authors

Quan Zhou^{1

2}, Man Lu², Guo-Sheng Li², Gan-Lu Peng², Yan-Feng Song¹

Affiliations

¹ Department of Gynecology and Obstetrics, The 900th Hospital of Joint Logistic Support Force, PLA, Fuzhou, Fujian, PR China.
² Department of Gynecology and Obstetrics, The First College of Clinical Medical Science, China Three Gorges University/Yichang Central People's Hospital, Yichang, 443000, PR China.

Abstract

Background: The pathogenesis of recurrent pelvic organ prolapse (POP) is currently unclear. Therefore, developing targeted preventive measures is difficult. This study identified potential key pathways, crucial genes, comorbidities, and therapeutic targets associated with the occurrence and development of recurrent POP.

Methods: The original microarray data GSE28660, GSE53868, and GSE12852 were downloaded from the GEO database. Identification and validation of differentially expressed genes (DEGs) and hub genes associated with recurrent POP were performed using R software and cytoHubba of Cytoscape. Protein-protein interaction (PPI) networks were constructed using the STRING tool and visualized using Cytoscape. Gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) enrichment analyses were effectively performed using DAVID platforms. In addition, the NetworkAnalyst platform was used to explore and visualize the miRNA-hub gene network, TF-hub gene network, hub gene-disease network, and hub gene-drug/chemical network.

Results: A total of 110 DEGs and 6 hub genes (ADIPOQ, IL6, PPARG, CEBPA, LPL, and LIPE) were identified in this study. These genes were primarily enriched in the PPAR, AMPK, and adipocytokine, non-alcoholic fatty liver disease, and signaling pathways related to glycerol metabolism. Moreover, 96 miRNAs and 97 TFs were identified to as being associated with recurrent POP. These genes were closely linked to adipocyte metabolism and distribution, energy metabolism, and the longevity regulatory pathway. In addition, 192 diseases or chronic complications were potentially related to the recurrence of POP, including diabetes, hypertension, obesity, inflammatory diseases, and chronic obstructive pulmonary disease. Furthermore, 954 drugs or compounds were shown to have therapeutic potential for recurrent POP, and the most critical target drugs were dexamethasone, bisphenol A, efavirenz, 1-methyl-3-isobutylxanthine, and estradiol.

Conclusions: The results of this study revealed that ADIPOQ, IL6, PPARG, CEBPA, LPL, and LIPE as potential hub genes associated with recurrent POP, and these hub genes may aid in the understanding of the mechanism underlying POP recurrence and the development of potential molecular drugs.

Keywords: Bioinformatic analysis; Differentially expressed genes; Pelvic organ prolapse; Recurrence; Therapeutic target.