# Serum metabolic fingerprinting for diagnosis and therapeutic applications of ovarian endometriosis

**Authors:** Chencheng Dai, Yiwei Cao, Yiran Xu, Moyuan Li, Guangquan Liu, Sujuan Xu, Nuo Ye, Changxiang Shi, Tiantian Fan, Pengfei Xu, Xuemei Jia

PMC · DOI: 10.1016/j.isci.2026.114887 · iScience · 2026-02-02

## TL;DR

This study identifies unique blood metabolites that can diagnose ovarian endometriosis and may offer new treatment options.

## Contribution

A non-invasive serum-based diagnostic panel and potential therapeutic metabolites for ovarian endometriosis are identified.

## Key findings

- Serum metabolic profiles are significantly altered in ovarian endometriosis patients.
- A diagnostic panel of serum metabolites can distinguish ovarian endometriosis from healthy controls.
- Three differential metabolites show therapeutic potential in an in vivo study.

## Abstract

Ovarian endometriosis (OvE) is a gynecological disorder with endometrial tissue in the ovaries, for which effective non-invasive diagnosis and curative treatments are currently lacking. Serum samples were collected from both discovery and validation cohorts to examine the metabolomic signatures. Fifty-six differential metabolites between patients with OvE and healthy controls were identified using untargeted metabolomic profiling. Weighted gene co-expression network analysis was further conducted to validate the differential metabolites. Subsequently, twenty-one metabolites were selected for further validation using targeted metabolomic profiling. Five machine learning algorithms confirmed the efficacy and stability of these metabolites for diagnosing OvE. Least absolute shrinkage and selection operator -logit regression identified six serum metabolites and two clinicopathological features with high diagnostic accuracy. Three differential metabolites were found to exhibit therapeutic potential for OvE in an in vivo study. Diagnostic, predictive, and therapeutic potential of serum metabolomes for OvE are provided in this study.

•Serum metabolic fingerprinting in OvE is significantly altered•A non-invasive diagnostic panel based on serum metabolic could distinguish OvE from HCs•Selected differential metabolites show potential therapeutic prospects for OvE

Serum metabolic fingerprinting in OvE is significantly altered

A non-invasive diagnostic panel based on serum metabolic could distinguish OvE from HCs

Selected differential metabolites show potential therapeutic prospects for OvE

Medicine; Reproductive medicine; Human metabolism

## Linked entities

- **Diseases:** ovarian endometriosis (MONDO:0006337)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** GGT1 (gamma-glutamyltransferase 1) [NCBI Gene 2678] {aka CD224, D22S672, D22S732, GGT, GGT 1, GGTD}, CYP19A1 (cytochrome P450 family 19 subfamily A member 1) [NCBI Gene 1588] {aka ARO, ARO1, CPV1, CYAR, CYP19, CYPXIX}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, CCL5 (C-C motif chemokine ligand 5) [NCBI Gene 6352] {aka D17S136E, RANTES, SCYA5, SIS-delta, SISd, TCP228}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, POTEF (POTE ankyrin domain family member F) [NCBI Gene 728378] {aka A26C1B, POTE2alpha, POTEACTIN}, BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}, Ptgs2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 29527] {aka COX-2, Cox2, PGHS-2, PHS II, Pghs2}, VIP (vasoactive intestinal peptide) [NCBI Gene 7432] {aka PHM27}, GPT (glutamic--pyruvic transaminase) [NCBI Gene 2875] {aka AAT1, ALT, ALT1, GPT1, SGPT}, NTF3 (neurotrophin 3) [NCBI Gene 4908] {aka HDNF, NGF-2, NGF2, NT-3, NT3}, COX2 (cytochrome c oxidase subunit II) [NCBI Gene 4513] {aka COII, MTCO2}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, NGF (nerve growth factor) [NCBI Gene 4803] {aka Beta-NGF, HSAN5, NGFB}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CEACAM3 (CEA cell adhesion molecule 3) [NCBI Gene 1084] {aka CD66D, CEA, CGM1, CGM1a, W264, W282}, GGTLC5P (gamma-glutamyltransferase light chain 5 pseudogene) [NCBI Gene 653590] {aka GGT}, AFP (alpha fetoprotein) [NCBI Gene 174] {aka AFPD, FETA, HPAFP}, MUC16 (mucin 16, cell surface associated) [NCBI Gene 94025] {aka CA125}, Vegfa (vascular endothelial growth factor A) [NCBI Gene 83785] {aka VEGF-A, VEGF111, VEGF164, VPF, Vegf}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, SLC17A5 (solute carrier family 17 member 5) [NCBI Gene 26503] {aka AST, ISSD, NSD, SD, SIALIN, SIASD}
- **Diseases:** metabolic disorders (MESH:D008659), OvE (MESH:D010049), chocolate cysts (MESH:D003560), adenomyosis (MESH:D062788), mood disorders (MESH:D019964), ASRM (MESH:C000719191), ectopic endometrial lesions (MESH:D014591), IBD (MESH:D015212), gynecological disorder (MESH:D005831), depression (MESH:D003866), endometriotic lesions (MESH:D009059), calcium oxalate lithiasis (MESH:C563477), hyperthyroidism (MESH:D006980), EAOC (MESH:D010051), cardiovascular disease (MESH:D002318), infection (MESH:D007239), hypoglycemia (MESH:D007003), Alzheimer's disease (MESH:D000544), infertility (MESH:D007246), cancer (MESH:D009369), diabetes (MESH:D003920), autism (MESH:D001321), APC (MESH:D011125), vitiligo (MESH:D014820), macrophages (MESH:D055501), anxiety (MESH:D001007), schizophrenia (MESH:D012559), chronic kidney disease (MESH:D051436), chronic inflammation (MESH:D007249), ovarian cysts (MESH:D010048), adenomatous polyps (MESH:D018256), HA (MESH:C537629), epilepsy (MESH:D004827), hypothyroidism (MESH:D007037), HC (MESH:D000067329), ectopic endometrium (MESH:D016889), pain (MESH:D010146), polycystic ovary syndrome (MESH:D011085), hypertension (MESH:D006973), pelvic pain (MESH:D017699), dysmenorrhea (MESH:D004412), Budd-Chiari syndrome (MESH:D006502), Endometriosis (MESH:D004715)
- **Chemicals:** GA (MESH:D005708), 3,3'-diaminobenzidine (MESH:D015100), biotin (MESH:D001710), glutamate (MESH:D018698), L-tryptophan (MESH:D014364), ascorbic acid (MESH:D001205), cholesterol (MESH:D002784), ketone bodies (MESH:D007657), ethanol (MESH:D000431), 5-hydroxytryptamine (MESH:D012701), quinic acid (MESH:D011801), short-chain fatty acid (MESH:D005232), glycine (MESH:D005998), auxin (MESH:D007210), beta-alanine (MESH:D015091), CO2 (MESH:D002245), citric acid (MESH:D019343), lipid (MESH:D008055), estradiol benzoate (MESH:C074283), TRIzol (MESH:C411644), E2 (MESH:D004958), benzoic acid (MESH:D019817), Lactic acid (MESH:D019344), isoleucine (MESH:D007532), AA (MESH:D000596), N-acetyl-aspartic acid (MESH:C000179), cocaine (MESH:D003042), triglycerides (MESH:D014280), arginine (MESH:D001120), paraffin (MESH:D010232), H2O2 (MESH:D006861), pyruvate (MESH:D019289), hippuric acid (MESH:C030514), CHOL (-), H&amp;E (MESH:D006371), melatonin (MESH:D008550), proline (MESH:D011392), TG (MESH:D013866), hematoxylin (MESH:D006416), gallic acid (MESH:D005707), penicillin (MESH:D010406)
- **Species:** gut metagenome (species) [taxon 749906], Rattus norvegicus (brown rat, species) [taxon 10116], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Hepatovirus A (no rank) [taxon 12092]
- **Mutations:** M20D
- **Cell lines:** OvE — Homo sapiens (Human), Ovarian adenocarcinoma, Cancer cell line (CVCL_A8KH)

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12930043/full.md

## References

74 references — full list in the complete paper: https://tomesphere.com/paper/PMC12930043/full.md

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Source: https://tomesphere.com/paper/PMC12930043