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Transcriptome and metabolome analyses reveal the interweaving of immune response and metabolic regulation in pelvic organ prolapse

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Abstract

Introduction and hypothesis

The pathogenesis of pelvic organ prolapse (POP) remains unknown. Herein, we aim to reveal the molecular profile of POP by transcriptomic and metabolomic analysis.

Methods

We selected 12 samples of uterosacral ligaments (USLs) from 6 POP patients and 6 controls for transcriptomic and metabolomic analyses. Differentially expressed genes (DEGs) were identified using the R package edgeR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using clusterProfiler, and a protein–protein interaction (PPI) network was constructed using STRING and visualized in Cytoscape. Metabolomic profiling was performed by a liquid chromatography–tandem mass spectrometry system.

Results

Transcriptomic analysis identified 487 DEGs between the POP and control groups. Functional enrichment analysis revealed that they were mostly related to immune response terms, including “adaptive immune response,” “T cell differentiation,” and “T cell activation.” In addition, PTPRC, LCK, CD247, IL2RB, CD2, CXR5, JUN, CD3E, IL2RG, and PRF1 were the 10 nodes with the highest node degrees in the PPI network. Metabolomic profiling revealed 290 differentially expressed metabolites, which significantly enriched in “glycerophospholipid metabolism,” “nicotinate and nicotinamide metabolism,” “glycine, serine, and threonine metabolism,” “arginine and proline metabolism,” “pyrimidine metabolism,” and “purine metabolism.” Finally, integrated analysis revealed that the DEGs involved in these significantly enriched metabolic pathways included NT5C1A, GMPR, SDS, ALAS2, CARNS1, PYCR1, P4HA3, PGS1, and NMRK2.

Conclusions

Our findings demonstrate that the immune response and metabolic regulatory pathways are intertwined in POP and might provide new therapeutic targets.

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Abbreviations

DEG:

Differentially expressed gene

ECM:

Extracellular matrix

FC:

Fold change

GO:

Gene Ontology

KEGG:

Kyoto Encyclopedia of Genes and Genomes

POP:

Pelvic organ prolapse

PPI:

Protein–protein interaction

USL:

Uterosacral ligament

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Acknowledgements

We thank all the participants, as well as all the volunteers who helped us to collect samples. We thank Nature Research Editing Service for English-language editing.

Funding

This project was supported by the Natural Science Foundation of Sichuan Province [grant number 2022NSFSC0815], the Yingcai Scheme, the Chengdu Women's and Children's Central Hospital [grant number YC2021004], the Youth Innovation Foundation of Sichuan Provincial Medical [grant number Q21060], and the Chengdu High-level Key Clinical Specialty Construction Project.

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Author notes

  1. Xia Yu and Ying Chen contributed equally to this work

Authors and Affiliations

  1. Department of Clinical Laboratory, Chengdu Women’s and Children’s Central Hospital, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China

    Xia Yu

  2. Department of Obstetrics and Gynecology, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, No.1617 Ri Yue Street, Chengdu, 610091, Sichuan, China

    Ying Chen, Li He & Yonghong Lin

  3. Department of Surgical, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China

    Hong Liu

  4. Sichuan Provincial Key Laboratory for Human Disease Gene Study and Institute of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, No.32 The First Ring Road West 2, Chengdu, 610071, Sichuan, China

    Zhenglin Yang

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Contributions

Z.L. Yang, Y.H. Lin: project development, management data analysis; X. Yu, Y. Chen: manuscript writing, statistical analysis; L. He, H. Liu: data collection.

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Correspondence to Zhenglin Yang or Yonghong Lin.

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Yu, X., Chen, Y., He, L. et al. Transcriptome and metabolome analyses reveal the interweaving of immune response and metabolic regulation in pelvic organ prolapse. Int Urogynecol J 34, 1395–1403 (2023). https://doi.org/10.1007/s00192-022-05357-5

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