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Single-Cell Transcriptomics Reveals Biomarkers for NK Cell Dysfunction in Endometriosis-Associated Immune

Wangshu Li1, Kexin Zhu1, Bowen Xu1

  • 1Department of Key Laboratory of Pediatric and Female Malignant Tumors, Dalian Women and Children's Medical Group, Dalian, China.

Mediators of Inflammation
|March 25, 2026
PubMed
Summary

Endometriosis involves immune dysregulation, particularly natural killer (NK) cell dysfunction. This study identifies granulysin (GNLY), perforin 1 (PRF1), and ENTPD1 as key genes in endometriosis pathogenesis and potential diagnostic biomarkers.

Keywords:
biomarkersendometriosisimmune dysregulationnatural killer cellssingle-cell RNA sequencing

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Area of Science:

  • Reproductive immunology
  • Molecular biology
  • Genomics

Background:

  • Endometriosis (EM) is characterized by immune dysregulation.
  • Natural killer (NK) cell dysfunction is a key factor in EM immune evasion and lesion growth.

Purpose of the Study:

  • To investigate the molecular mechanisms of immune dysregulation in endometriosis.
  • To identify potential diagnostic biomarkers and therapeutic targets for EM.

Main Methods:

  • Single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq integration.
  • Machine learning algorithms (LASSO, SVM-RFE) for feature selection.
  • Validation of gene expression and functional assays for cell migration and invasiveness.

Main Results:

  • Identified 11 cell clusters and eight major cell types.
  • Prioritized 20 differentially expressed genes (DEGs) and identified GNLY, PRF1, and ENTPD1 as key genes.
  • Demonstrated ENTPD1's dual role in immunomodulation and promoting stromal cell migration via adenosine signaling.

Conclusions:

  • NK cell dysfunction is central to endometriosis pathogenesis.
  • GNLY, PRF1, and ENTPD1 are proposed as potential diagnostic biomarkers for EM.
  • ENPTD1 offers a mechanistic rationale for targeted therapies by modulating immune cells and stromal activity.