# sMICA/sMICB and Immune Checkpoint in Endometriosis: Toward a Minimally Invasive Diagnostic Model Based on Machine Learning

**Authors:** Anastasia Belevich, Maria Yarmolinskaya, Ilya Smirnov, Anastasia Stolbovaya, Olga Shashkova, Marina Samoylovich, Sergey Selkov, Polina Grebenkina, Elizaveta Tyshchuk, Dmitry Sokolov

PMC · DOI: 10.3390/biomedicines14030647 · Biomedicines · 2026-03-12

## TL;DR

This study explores immune markers in endometriosis and proposes a machine learning model for a less invasive diagnosis.

## Contribution

A novel machine learning-based diagnostic model for endometriosis using immune markers and patient data.

## Key findings

- sMICB levels in peritoneal fluid differ by endometriosis stage and adhesion presence.
- sMICA levels in peritoneal fluid are elevated in infertility-related endometriosis.
- XGBoost model outperformed logistic regression with higher accuracy and AUC for endometriosis diagnosis.

## Abstract

Background: Endometriosis is a complex condition that impairs women’s quality of life and reproductive potential. Its diagnosis remains significant challenge for clinicians. The aim of the study was to investigate cancer-like immune evasion mechanisms in endometriosis and to develop a novel diagnostic model using machine learning. Methods: In this study, we measured the levels of soluble forms of the following immune markers in blood serum and peritoneal fluid (PF): sMICA, sMICB, sEng, sCD25, s4-1BB, sB7.2, sCTLA-4, sPD-L1, sPD-1, sTIM-3, sLAG-3, and sGal-9. Results: sMICB levels in PF differed across endometriosis stages and were higher in patients with endometriosis-associated adhesions. sMICA levels in PF were elevated in women with endometriosis-associated infertility. The disease severity was inversely correlated with serum sB7.2 levels and positively correlated with serum sTIM-3 levels. A logistic regression model achieved an accuracy = 0.79, AUC = 0.94, and F1-score = 0.88, whereas XGBoost performed better with accuracy = 0.94, AUC = 0.95, and F1-score = 0.96. The key predictive features in both models were sMICB serum level and patients’ pain score. Conclusions: Our results demonstrate the potential role of sMICA and sMICB shedding in endometriosis and present a novel, minimally invasive diagnostic approach.

## Linked entities

- **Proteins:** Ctla4 (cytotoxic T-lymphocyte-associated protein 4), SPDL1 (spindle apparatus coiled-coil protein 1), HOXD13 (homeobox D13)
- **Diseases:** endometriosis (MONDO:0005133)

## Full-text entities

- **Genes:** SPDL1 (spindle apparatus coiled-coil protein 1) [NCBI Gene 54908] {aka CCDC99}, HOXD13 (homeobox D13) [NCBI Gene 3239] {aka BDE, BDSD, HOX4I, SPD, SPD1}
- **Diseases:** cancer (MESH:D009369), Endometriosis (MESH:D004715), pain (MESH:D010146), infertility (MESH:D007246)
- **Chemicals:** sMICB (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13023530/full.md

## References

36 references — full list in the complete paper: https://tomesphere.com/paper/PMC13023530/full.md

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Source: https://tomesphere.com/paper/PMC13023530