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Bioinformatically deciphering immune cell infiltration and signature genes in pelvic organ prolapse

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Abstract

Introduction and hypothesis

The study is aimed at bioinformatically deciphering immune cell infiltration, signature genes, and their correlations in POP.

Methods

Three microarray datasets were included. Matrixes representing the uterosacral ligament were merged as a test matrix and the others representing vaginal tissues were merged as a validation matrix. The single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm was performed to evaluate immune cell infiltration. Correlations among differential immune cells were revealed by Spearman’s rank correlation. Differentially expressed genes (DEGs) were screened by both “Batch correction” and “RobustRankAggreg” methods. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes were conducted for functional analysis. Hub genes were identified through cytoHubba of Cytoscape, and further validated by a validation matrix and clinical samples as signature genes. Correlations of differential immune cells with signature genes were analyzed by Spearman’s rank correlation.

Results

Five differential immune cells (macrophages, monocytes, regulatory T cell [Treg], type 1 T cell [Th1], and natural killer T cells [NKT]) were identified and eight pairs of immune cells had significant correlations. Screened 230 DEGs were extracellular matrix (ECM) and immune related. Eleven hub genes were initially identified and five of them (LOX, IL-6, SDC1, ICAM1, and CD38) were validated as signature genes. Significant correlations of differential immune cells with signature genes were shown in twelve pairs, especially Th1–IL6, NKT–IL6, Th1–ICAM1, macrophage–IL6, and macrophage–LOX pairs.

Conclusions

Pelvic organ prolapse could be considered immune related. Significantly infiltrated immune cells may contribute to the development of POP through close involvement with ECM- and immune-related signature genes.

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Data availability

The datasets (GSE28660, GSE12852, GSE53868) analyzed in the study are publicly available from the GEO DataSets (https://www.ncbi.nlm.nih.gov/).

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Acknowledgement

We are grateful for the GEO database and all suppliers who uploaded datasets of GSE28660, GSE12852, GSE151188.

Funding

This work was supported by the National Natural Science Foundation of China (No. 82071630 and 81771560 granted to X. Tong; No. 81702745 granted to Y. Yang; No. 81873827 granted to Y. Guo); Tongji Hospital National Natural Science Foundation Training Project (No. GJPY2119 granted to X. Tong). The funding organizations did not contribute to any of the following: design of the study, data collection, data analysis, interpretation of data, and writing the manuscript or decision to publish.

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Author notes

  1. Chenghao Wu and Zixuan Zhou contributed equally to this work

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Tongji Hospital, Tongji University School of Medicine, No.389 Xincun Road, Shanghai, 200065, People’s Republic of China

    Chenghao Wu, Yuanyuan Yang, Huaifang Li, Yi Guo & Xiaowen Tong

  2. Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Burn Institute of PLA, Shanghai, 200433, People’s Republic of China

    Zixuan Zhou

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  1. Chenghao Wu
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Contributions

C. Wu: manuscript writing, bioinformatics analysis; Z. Zhou: experiment performance and data analysis; Y. Yang and H. Li: sample collection; G. Yi: manuscript revision; X. Tong: project development and manuscript revision.

Corresponding authors

Correspondence to Yi Guo or Xiaowen Tong.

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Ethics approval

The study protocol was approved by the Ethics Committee of Tongji Hospital, Tongji University School of Medicine (Number: K-2021-1115). All participants received the written informed consent.

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Wu, C., Zhou, Z., Yang, Y. et al. Bioinformatically deciphering immune cell infiltration and signature genes in pelvic organ prolapse. Int Urogynecol J 34, 1091–1101 (2023). https://doi.org/10.1007/s00192-022-05378-0

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  • DOI: https://doi.org/10.1007/s00192-022-05378-0

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