The NLRP3 activation-related signature predict the diagnosis and indicate immune characteristics in endometriosis

Weihua Nong, Huimei Wei, Sheng Dou, Liqiao He, Tianlong Li, Luping Lin, Bixiao Wei, Shun Zhang, Peng Huo, Mingyou Dong
In: Research Square · 2023 · doi:10.21203/rs.3.rs-2830815/v1 · W4368375978
preprint OA: green CC0
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⚙ AI-generated summary by claude@2026-06, 2026-06-06 ⓘ

This study identified four key NLRP3 activation-related genes (NLRP3, IL-1β, LY96, and PDIA3) that accurately diagnose endometriosis and may indicate immune characteristics, with niclosamide suggested as a potential treatment.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-06 ⓘ

This preprint investigates NLRP3 activation-related genes in endometriosis using publicly available endometrial transcriptomic datasets (GSE7307, GSE7305, and GSE23339) to identify differentially expressed genes and functional enrichment, then applies random forest and SVM-RFE to select four diagnostic markers (NLRP3, IL-1β, LY96, PDIA3) and build a diagnostic model whose performance is assessed by AUC. The marker selection is experimentally supported by western blotting in endometrial tissues from 12 surgically treated patients (ovarian endometriosis cysts and matched non-endometriosis controls) and is further validated across the additional GEO datasets, with immune cell infiltration and immune-marker correlations analyzed in relation to the candidate genes. A key limitation is that the work relies on small sample sizes in the discovery/validation cohorts and uses a preprint framework, and it explicitly calls for large-scale, multicenter prospective studies to confirm diagnostic value in blood samples. This paper is centrally about endometriosis — it focuses on NLRP3 activation-related gene signatures to derive and validate diagnostic biomarkers and related immune characteristics in endometriosis.

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Abstract

Abstract Endometriosis (EMS) is a common gynecological disease leading to chronic pelvic pain and infertility in women of reproductive age, but its underlying pathogenic genes and effective treatment are still unclear. To date, abnormal expression of NLRP3 activation-related genes has been identified in EMS patients and mouse models. Therefore, this study sought to identify the key genes that could affect the diagnosis and treatment of EMS. The GSE7307 dataset was downloaded from the Gene Expression Omnibus (GEO) database, including 18 EMS samples and 23 control samples. 14 differential genes related to NLRP3 activation and EMS were obtained from the endometrial samples of GSE7307 by differential analysis. GO and KEGG analysis showed that these genes were mainly involved in the production and regulation of the cytokine IL-1β, and the NOD-like receptor signaling pathway. Random Forest (RF) and support vector machine recursive feature elimination (SVM-RFE) algorithms were used to select four diagnostic markers related to NLRP3 activation (NLRP3, IL-1β, LY96 and PDIA3) to construct the EMS diagnostic model. The four diagnostic markers were verified using western blotting and validated in the GSE7305 and GSE23339 datasets. The AUC values showed that the model had a good diagnostic performance. In addition, the infiltration of immune cells in the samples and the correlation between different immune factors and diagnostic markers were further discussed. These results suggest that four diagnostic markers may also play an important role in the immunity of EMS. Finally, 10 drugs targeting to four diagnostic markers were retrieved from the DrugBank database, of which niclosamide proved useful for treating EMS. Overall, we identified four key diagnostic genes for EMS. In addition, large-scale and multicenter prospective cohort studies are necessary to confirm whether these four genes also have valid diagnostic value in blood samples from EMS patients.

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Condition tags

endometriosischronic_pelvic_paininfertility

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References (52)

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