# Systemic Oxidative Stress Markers in Endometriosis: Elevated Advanced Glycation End Products and Sestrin 2 in Women with Ovarian Endometrioma

**Authors:** Nura Fitnat Topbas Selcuki, Kubra Bagci, Feyza Nur Tuncer, Cihan Kaya, Salih Yilmaz, Pinar Yalcin Bahat

PMC · DOI: 10.3390/biomedicines14020405 · Biomedicines · 2026-02-10

## TL;DR

The study finds that women with ovarian endometrioma have higher levels of oxidative stress markers AGEs and SESN2, suggesting these could be useful diagnostic biomarkers.

## Contribution

This is the first study to show elevated systemic AGEs and SESN2 in ovarian endometrioma, identifying SESN2 as a promising biomarker candidate.

## Key findings

- Serum AGEs and SESN2 levels were significantly higher in women with ovarian endometrioma compared to healthy controls.
- SESN2 demonstrated high diagnostic accuracy with 87.39% sensitivity and 86.05% specificity for detecting endometrioma.

## Abstract

Background/Objectives: Endometriosis is a chronic inflammatory disease characterized by ectopic endometrial tissue growth and is strongly associated with oxidative stress; however, systemic biomarkers reflecting this stress response remain limited. Advanced glycation end products (AGEs) promote oxidative and inflammatory signaling, while sestrin 2 (SESN2) is a stress-inducible protein involved in cellular redox homeostasis. This prospective case–control study aimed to evaluate serum AGEs and SESN2 levels in women with ovarian endometrioma and to assess their diagnostic performance. Methods: A total of 80 reproductive-aged women were enrolled, including 37 patients with ultrasonographically confirmed ovarian endometrioma and 43 healthy controls. Serum AGEs and SESN2 concentrations were measured using enzyme-linked immunosorbent assay. Results: Both biomarkers were significantly elevated in patients compared with controls (AGEs: 110.11 ± 33.35 vs. 91.70 ± 41.82 ng/mL, p = 0.007; SESN2: 9.32 ± 2.59 vs. 5.57 ± 1.52 ng/mL, p < 0.001). Receiver operating characteristic analysis demonstrated modest discriminatory ability for AGEs (AUC = 0.656), whereas SESN2 showed high diagnostic accuracy (AUC = 0.893), with 87.39% sensitivity and 86.05% specificity at an optimal cut-off value. Neither AGEs nor SESN2 levels were associated with lesion size, laterality, or pain symptoms. Conclusions: These findings provide the first evidence that circulating AGEs and SESN2 are elevated in ovarian endometrioma, supporting the role of systemic oxidative stress and stress-response pathways in endometriosis. SESN2, in particular, emerges as a promising biomarker candidate for disease presence, warranting further validation in larger and more diverse endometriosis cohorts.

## Linked entities

- **Proteins:** SESN2 (sestrin 2)
- **Diseases:** endometriosis (MONDO:0005133)

## Full-text entities

- **Genes:** NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, MAP1LC3A (microtubule associated protein 1 light chain 3 alpha) [NCBI Gene 84557] {aka ATG8E, LC3, LC3A, MAP1ALC3, MAP1BLC3}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, RPTOR (regulatory associated protein of MTOR complex 1) [NCBI Gene 57521] {aka KOG1, Mip1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, PRKN (parkin RBR E3 ubiquitin protein ligase) [NCBI Gene 5071] {aka AR-JP, LPRS2, PARK2, PDJ}, PINK1 (PTEN induced kinase 1) [NCBI Gene 65018] {aka BRPK, PARK6}, SESN3 (sestrin 3) [NCBI Gene 143686] {aka SEST3}, TSC2 (TSC complex subunit 2) [NCBI Gene 7249] {aka LAM, PPP1R160, TSC4}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, ULK1 (unc-51 like autophagy activating kinase 1) [NCBI Gene 8408] {aka ATG1, ATG1A, UNC51, Unc51.1, hATG1}, AGER (advanced glycosylation end-product specific receptor) [NCBI Gene 177] {aka RAGE, SCARJ1, sRAGE}, ATP5PF (ATP synthase peripheral stalk subunit F6) [NCBI Gene 522] {aka ATP5, ATP5A, ATP5J, ATPM, CF6, F6}, RENBP (renin binding protein) [NCBI Gene 5973] {aka RBP, RNBP}, SQSTM1 (sequestosome 1) [NCBI Gene 8878] {aka A170, DMRV, EBIAP, FTDALS3, NADGP, OSIL}, BECN1 (beclin 1) [NCBI Gene 8678] {aka ATG6, VPS30, beclin1}, SESN2 (sestrin 2) [NCBI Gene 83667] {aka HI95, SES2, SEST2}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, KEAP1 (kelch like ECH associated protein 1) [NCBI Gene 9817] {aka INrf2, KLHL19}, SESN1 (sestrin 1) [NCBI Gene 27244] {aka PA26, SEST1}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, PRKAA1 (protein kinase AMP-activated catalytic subunit alpha 1) [NCBI Gene 5562] {aka AMPK, AMPK alpha 1, AMPKa1}
- **Diseases:** gestational diabetes (MESH:D016640), Adenomyosis (MESH:D062788), hemolysis (MESH:D006461), peritoneal or deep infiltrating disease (MESH:D010532), Endometriosis (MESH:D004715), Pain (MESH:D010146), hyperglycemia (MESH:D006943), inflammation (MESH:D007249), injury to (MESH:D014947), myoma (MESH:D009214), uterine leiomyomas (OMIM:150699), preeclampsia (MESH:D011225), cancer (MESH:D009369), diabetes (MESH:D003920), inflammatory, hepatic, renal, or neurological disease (MESH:D018746), leiomyoma (MESH:D007889), endometrial polyps (MESH:D014591), cyst (MESH:D003560), CPP (MESH:D011472), endothelial (MESH:D005642), Ovarian Endometrioma (MESH:D010049), pelvic pain (MESH:D017699), dysmenorrhea (MESH:D004412), colorectal and bladder malignancies (MESH:D015179), hyperglycemic (MESH:D006944), polycystic ovary syndrome (MESH:D011085), insulin resistance (MESH:D007333), infertility (MESH:D007246), immune dysfunction (MESH:D007154), cardiovascular disease (MESH:D002318), dyspareunia (MESH:D004414)
- **Chemicals:** iron (MESH:D007501), AGEs (MESH:D017127), Schiff bases (MESH:D012545), hydroxyl radicals (MESH:D017665), CML (MESH:C048496), sugars (MESH:D000073893), polyol (MESH:C024617), lipids (MESH:D008055), thiazolidinediones (MESH:D045162), ROS (MESH:D017382), superoxides (MESH:D013481), dicarbonyl compounds (-)
- **Species:** Meleagris gallopavo (common turkey, species) [taxon 9103], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

31 references — full list in the complete paper: https://tomesphere.com/paper/PMC12937960/full.md

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Source: https://tomesphere.com/paper/PMC12937960