# Exosome-Enriched Hub Gene Networks Identify Diagnostic Biomarkers and Repurposable Therapeutic Targets in Endometriosis

**Authors:** Meng-Hsiu Tsai, Shao-Ping Weng, Li-Jen Su, Tsung-Hsuan Lai

PMC · DOI: 10.3390/ijms27062572 · International Journal of Molecular Sciences · 2026-03-11

## TL;DR

This study identifies key genes and biological pathways in endometriosis that could lead to new non-invasive tests and repurposed drugs.

## Contribution

The paper introduces an 11-gene hub network linked to immune, adhesion, and angiogenesis processes in endometriosis.

## Key findings

- 262 genes were identified as consistently differentially expressed across endometriosis datasets.
- 11 hub genes form an immune-adhesion-angiogenesis axis central to endometriosis pathology.
- 63 genes are exosome-associated, suggesting potential for non-invasive liquid biopsy tests.

## Abstract

Endometriosis is a heterogeneous chronic inflammatory disorder associated with substantial diagnostic delay and limited therapeutic options, highlighting the need of robust non-invasive biomarkers and actionable molecular targets to complement existing low-sensitivity tests. To identify conserved pathogenic mechanisms with translational potential, here, we uniformly reprocessed three independent the Gene Expression Omnibus (GEO) microarray cohorts (GSE7305, GSE25628, and GSE11691) and applied a strict, directionally consistent intersection strategy to identify conserved transcriptional signals. We identified 262 consensus differentially expressed genes enriched for immunity/inflammation, cell adhesion and migration, and angiogenesis, consistent with key biological hallmarks of lesion establishment and persistence. Protein–protein interaction topology prioritized 11 highly connected hub genes (VCAM1, CCL2, MCAM, CD14, CD24, FGFR1, SIRPA, CSF1R, S100A9, S100A8, and LY96) that likely act as an integrated immune-adhesion-angiogenesis axis. Notably, 63/262 (24%) of the consensus genes were annotated to the extracellular exosome compartment, supporting their translational relevance as liquid-biopsy candidates. Finally, connectivity mapping using the LINCS L1000 framework nominated small-molecule perturbagens predicted to reverse the endometriosis-associated signature, providing a rational starting point for drug-repurposing experiments. In conclusion, this study elucidates a conserved immune–adhesion–angiogenesis axis driven by an 11-gene hub network in endometriosis. These core regulators represent promising candidates for the development of non-invasive liquid biopsies and precision, non-hormonal therapeutics.

## Linked entities

- **Genes:** VCAM1 (vascular cell adhesion molecule 1) [NCBI Gene 7412], CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347], MCAM (melanoma cell adhesion molecule) [NCBI Gene 4162], CD14 (CD14 molecule) [NCBI Gene 929], CD24 (CD24 molecule) [NCBI Gene 100133941], FGFR1 (fibroblast growth factor receptor 1) [NCBI Gene 2260], SIRPA (signal regulatory protein alpha) [NCBI Gene 140885], CSF1R (colony stimulating factor 1 receptor) [NCBI Gene 1436], S100A9 (S100 calcium binding protein A9) [NCBI Gene 6280], S100A8 (S100 calcium binding protein A8) [NCBI Gene 6279], LY96 (lymphocyte antigen 96) [NCBI Gene 23643]
- **Diseases:** endometriosis (MONDO:0005133)

## Full-text entities

- **Genes:** LY96 (lymphocyte antigen 96) [NCBI Gene 23643] {aka ESOP-1, MD-2, MD2, ly-96}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, FGFR1 (fibroblast growth factor receptor 1) [NCBI Gene 2260] {aka BFGFR, CD331, CEK, ECCL, FGFBR, FGFR-1}, CD14 (CD14 molecule) [NCBI Gene 929], SIRPA (signal regulatory protein alpha) [NCBI Gene 140885] {aka BIT, CD172A, MFR, MYD-1, MYD1, P84}, CD24 (CD24 molecule) [NCBI Gene 100133941] {aka CD24A}, MCAM (melanoma cell adhesion molecule) [NCBI Gene 4162] {aka CD146, HEMCAM, METCAM, MUC18, MelCAM}, VCAM1 (vascular cell adhesion molecule 1) [NCBI Gene 7412] {aka CD106, INCAM-100}, S100A9 (S100 calcium binding protein A9) [NCBI Gene 6280] {aka 60B8AG, CAGB, CFAG, CGLB, L1AG, LIAG}, S100A8 (S100 calcium binding protein A8) [NCBI Gene 6279] {aka 60B8AG, CAGA, CFAG, CGLA, CP-10, L1Ag}, CSF1R (colony stimulating factor 1 receptor) [NCBI Gene 1436] {aka BANDDOS, C-FMS, CD115, CSF-1R, CSFR, FIM2}
- **Diseases:** inflammation (MESH:D007249), Endometriosis (MESH:D004715)

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13026275/full.md

## References

84 references — full list in the complete paper: https://tomesphere.com/paper/PMC13026275/full.md

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Source: https://tomesphere.com/paper/PMC13026275