Integrative analysis reveals ferroptosis-related genes with RRM2 as a key driver in endometriosis

Lanping Zhong, Yuhong Niu, Rui Ma, Yuting Luo, Xin Li, Qiru Wang, Hongxia Xu, Xiaomin Kang
Gene · 2025 · vol. 970 , pp. 149754 · doi:10.1016/j.gene.2025.149754 · PMID:40939963 · W4414107475
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

This study identified ferroptosis-related genes, with RRM2 highlighted as a key driver, in the context of endometriosis through integrative analysis.

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Abstract

BACKGROUND: Endometriosis is an estrogen-dependent disorder with unclear molecular mechanisms. Ferroptosis, a regulated iron-dependent cell death, may play a key role, yet the specific genes involved remain underexplored. METHODS: Ferroptosis-related genes (FRGs) were identified in endometriosis using GEO data, with key genes selected through LASSO, SVM-RFE, and cross-tabulation analysis. We validated gene expression in the tissues of patients with endometriosis using quantitative real-time polymerase chain reaction (qRT-PCR) and assessed the causal effects of these genes on endometriosis subtypes through Mendelian randomization (MR). We further validated the causal relationship between FRGs with diagnostic value and the progression of endometriosis through in vitro and in vivo experiments. RESULTS: We identified 13 differentially expressed ferroptosis-related genes (DE-FRGs) in endometriosis, including six upregulated and seven downregulated genes. Among these, FZD7, HMOX1, HSPA5, TFAP2C, and RRM2 were identified as key genes with diagnostic potential (AUC =0.91). MR analysis revealed that FZD7, HMOX1, RRM2, and HSPA5 were causally associated with different subtypes of endometriosis, with FZD7 acting as a protective factor (OR  1). Notably, RRM2 exhibited causal associations across multiple subtypes of the disease. qRT-PCR confirmed significant upregulation of RRM2 in ectopic endometrial tissues (P < 0.01). Functional validation experiments further demonstrated that RRM2 enhances the invasiveness of endometrial cells in vitro (P＜0.05), while in vivo, RRM2 overexpression induced endometriosis-like phenotypes in a mouse model. CONCLUSION: Our integrative analysis combining transcriptomic profiling, MR, and experimental validation identified FRGs, particularly RRM2, as being causally associated with endometriosis. RRM2 may contribute to disease progression and represents a promising target for diagnosis and therapy.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (59)

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