External validation of putative biomarkers in eutopic endometrium of women with endometriosis using NanoString technology

article OA: green CC0 ⤵ 4 in-corpus citations
AI-generated summary by claude@2026-06+body, 2026-06-12

This study used NanoString technology to analyze nine candidate biomarkers in endometrial biopsies from women with and without endometriosis, finding that FOS, MMP7, and MMP11 were important for classification.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

AI-generated deep summary by claude@2026-06, 2026-06-12 · read from full text

This study evaluated whether a combined set of nine eutopic endometrial gene biomarkers (selected from the literature and independent of cycle phase) could classify endometriosis using NanoString. Endometrial biopsies from 109 women with endometriosis (including deep infiltrating and ovarian forms) and 110 controls were analyzed by comparing differentially expressed genes and fitting generalized linear models to build a disease classifier. The models identified 68% of women with endometriosis but did not reliably distinguish individual endometriosis types from controls, and from the nine genes, FOS, MMP7, and MMP11 were highlighted as important (with FOS most over-expressed). This paper is centrally about endometriosis—external validation of eutopic endometrial gene expression biomarkers (FOS, MMP7, MMP11) using NanoString to classify endometriosis.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Abstract

PurposeTo combine different independent endometrial markers to classify the presence of endometriosis.MethodsEndometrial biopsies were obtained from 109 women with endometriosis as well as 110 control women. Nine candidate biomarkers independent of cycle phase were selected from the literature and NanoString was performed. We compared differentially expressed genes between groups and generated generalized linear models to find a classifier for the disease.ResultsGeneralized linear models correctly detected 68% of women with endometriosis (combining deep infiltrating and ovarian endometriosis). However, we were not able to distinguish between individual types of endometriosis compared to controls. From the 9 tested genes, FOS, MMP7, and MMP11 seem to be important for disease classification, and FOS was the most over-expressed gene in endometriosis.Conclusion(s)Although generalized linear models may allow identification of endometriosis, we did not obtain perfect classification with the selected gene candidates.
Full text 10,822 characters · extracted from oa-doi-fallback · 4 sections · click to expand

Abstract

Purpose To combine different independent endometrial markers to classify the presence of endometriosis.

Methods

Endometrial biopsies were obtained from 109 women with endometriosis as well as 110 control women. Nine candidate biomarkers independent of cycle phase were selected from the literature and NanoString was performed. We compared differentially expressed genes between groups and generated generalized linear models to find a classifier for the disease.

Results

Generalized linear models correctly detected 68% of women with endometriosis (combining deep infiltrating and ovarian endometriosis). However, we were not able to distinguish between individual types of endometriosis compared to controls. From the 9 tested genes, FOS, MMP7, and MMP11 seem to be important for disease classification, and FOS was the most over-expressed gene in endometriosis. Conclusion(s) Although generalized linear models may allow identification of endometriosis, we did not obtain perfect classification with the selected gene candidates. Similar content being viewed by others

References

Evans J, Salamonsen LA. Inflammation, leukocytes and menstruation. Rev Endocr Metab Disord. 2012;13:277–88. Zondervan KT, Becker CM, Koga K, Missmer SA, Taylor RN, Viganò P. Endometriosis. Nat Rev Dis Primers. 2018;4:9. Selçuk I, Bozdaǧ G. Recurrence of endometriosis; risk factors, mechanisms and biomarkers; review of the literature. J Turk Ger Gynecol Assoc. 2013;14:98–103. Prescott J, Farland LV, Tobias DK, Gaskins AJ, Spiegelman D, Chavarro JE, et al. A prospective cohort study of endometriosis and subsequent risk of infertility. Hum Reprod. 2016;31:1475–82. Nnoaham KE, Hummelshoj L, Webster P, d’Hooghe T, de Cicco Nardone F, de Cicco Nardone C, et al. Reprint of: Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries. Fertil Steril. 2019;112:e137–52. Wykes CB, Clark TJ, Khan KS. Accuracy of laparoscopy in the diagnosis of endometriosis: a systematic quantitative review. BJOG. 2004;111:1204–12. Moore J, Copley S, Morris J, Lindsell D, Golding S, Kennedy S. A systematic review of the accuracy of ultrasound in the diagnosis of endometriosis. Ultrasound Obstet Gynecol. 2002;20:630–4. Guerriero S, Saba L, Pascual MA, Ajossa S, Rodriguez I, Mais V, et al. Transvaginal ultrasound vs magnetic resonance imaging for diagnosing deep infiltrating endometriosis: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2018;51:586–95. Noventa M, Scioscia M, Schincariol M, Cavallin F, Pontrelli G, Virgilio B, et al. Imaging modalities for diagnosis of deep pelvic endometriosis: comparison between trans-vaginal sonography, rectal endoscopy sonography and magnetic resonance imaging. A Head-to-Head meta-analysis. Diagnostics. 2019;9(4):225. Guerriero S, Ajossa S, Minguez JA, Jurado M, Mais V, Melis GB, et al. Accuracy of transvaginal ultrasound for diagnosis of deep endometriosis in uterosacral ligaments, rectovaginal septum, vagina and bladder: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2015;46:534–45. Guerriero S, Ajossa S, Orozco R, Perniciano M, Jurado M, Melis GB, et al. Accuracy of transvaginal ultrasound for diagnosis of deep endometriosis in the rectosigmoid: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2016;47:281–9. Fassbender A, Burney RO, Dorien FO, D’Hooghe T, Giudice L. Update on biomarkers for the detection of endometriosis. Biomed Res Int. Hindawi Publishing Corporation. 2015;2015:130854 Irungu S, Mavrelos D, Worthington J, Blyuss O, Saridogan E, Timms JF. Discovery of non-invasive biomarkers for the diagnosis of endometriosis. Clin Proteomics BioMed Central. 2019;16:1–16. Ahn SH, Singh V, Tayade C. Biomarkers in endometriosis: challenges and opportunities. Fertil Steril. 2017;107:523–32. Kim JJ, Lessey BA. Endometrial receptivity in eutopic endometrium of women with endometriosis it is affected, let me show you why. Fertil Steril. 2017;108:19–27. Aghajanova L, Velarde MC, Giudice LC. Altered gene expression profiling in endometrium: evidence for progesterone resistance. Semin Reprod Med. 2010;28:51–8. Kojima K, April C, Canasto-Chibuque C, Chen X, Deshmukh M, Venkatesh A, et al. Transcriptome profiling of archived sectioned formalin-fixed paraffin-embedded (AS-FFPE) tissue for disease classification. PLoS One. 2014;9:1–7. Geiss GK et al., “Direct multiplexed measurement of gene expression with color-coded probe pairs”. Nat Biotech 2008;26(3):317- 325. Veldman-Jones MH, Brant R, Rooney C, Geh C, Emery H, Harbron CG, et al. Evaluating robustness and sensitivity of the nanostring technologies ncounter platform to enable multiplexed gene expression analysis of clinical samples. Cancer Res. 2015;75:2587–93. Zhao L, Gu C, Ye M, Zhang Z, Han W, Fan W, et al. Identification of global transcriptome abnormalities and potential biomarkers in eutopic endometria of women with endometriosis: a preliminary study. Biomed Rep. 2017;6:654–62. Matsuzaki S, Maleysson E, Darcha C. Analysis of matrix metalloproteinase-7 expression in eutopic and ectopic endometrium samples from patients with different forms of endometriosis. Hum Reprod. 2010;25:742–50. Ruiz LA, Báez-Vega PM, Ruiz A, Peterse DP, Monteiro JB, Bracero N, et al. Dysregulation of lysyl oxidase expression in lesions and endometrium of women with endometriosis. Reprod Sci. 2015;22:1496–508. Herndon CN, Aghajanova L, Balayan S, Erikson D, Barragan F, Goldfien G, et al. Global transcriptome abnormalities of the eutopic endometrium from women with adenomyosis. Reprod Sci. 2016;23:1289–303. Henze D, Doecke WD, Hornung D, Agueusop I, Von Ahsen O, Machens K, et al. Endometriosis leads to an increased trefoil factor 3 concentration in the peritoneal cavity but does not alter systemic levels. Reprod Sci. 2017;24:258–67. Suzumori N, Sato M, Yoneda T, Ozaki Y, Takagi H, Suzumori K. Expression of secretory leukocyte protease inhibitor in women with endometriosis. Fertil Steril. 1999;72:857–67. Ray K, Fahrmann J, Mitchell B, Paul D, King H, Crain C, et al. Oxidation-sensitive nociception involved in endometriosis-associated pain. Pain. 2015;156:528–39. Wu Y, Kajdacsy-Balla A, Strawn E, Basir Z, Halverson G, Jailwala P, et al. Transcriptional characterizations of differences between eutopic and ectopic endometrium. Endocrinology. 2006;147:232–46. Poli-Neto, O.B., Meola, J., Rosa-e-Silva, J.C. et al. Transcriptome meta-analysis reveals differences of immune profile between eutopic endometrium from stage I-II and III-IV endometriosis independently of hormonal milieu. Sci Rep. 2020;10(1):313. Tamaresis JS, Irwin JC, Goldfien GA, Rabban JT, Burney RO, Nezhat C, et al. Molecular classification of endometriosis and disease stage using high-dimensional genomic data. Endocrinology. 2014;155:4986–99. Pan H, Sheng JZ, Tang L, Zhu R, Zhou TH, Huang HF. Increased expression of c-fos protein associated with increased matrix metalloproteinase-9 protein expression in the endometrium of endometriotic patients. Fertil Steril. 2008;90:1000–7. Morsch DM, Carneiro MM, Lecke SB, Araújo FC, Camargos AF, Reis FM, et al. C-fos gene and protein expression in pelvic endometriosis: a local marker of estrogen action. J Mol Histol. 2009;40:53–8. Milde-Langosch K. The Fos family of transcription factors and their role in tumourigenesis. Eur J Cancer. 2005;41:2449–61. Milde-Langosch K, Röder H, Andritzky B, Aslan B, Hemminger G, Brinkmann A, et al. The role of the AP-1 transcription factors c-Fos, FosB, Fra-1 and Fra-2 in the invasion process of mammary carcinomas. Breast Cancer Res Treat. 2004;86:139–52. Dong C, Ye DX, Zhang WB, Pan HY, Zhang ZY, Zhang L. Overexpression of c-fos promotes cell invasion and migration via CD44 pathway in oral squamous cell carcinoma. J Oral Pathol Med. 2015;44:353–60. Gómez-Macías GS, Garza-Rodríguez ML, Garza-Guajardo R, Monsiváis-Ovalle D, Ancer-Rodríguez J, Barrera-Saldaña HA, et al. Overexpression of the matrix metalloproteinase 11 gene is a potential biomarker for type 1 endometrial cancer. Oncol Lett. 2018;16:1073–8. Henriet P, Mon KS, Marbaix E. Are matrix metalloproteinases and their inhibitors reliable diagnosis biomarkers and attractive therapeutic targets in endometriosis? Met Med. 2016;3:81–92. Chatterjee K, Jana S, DasMahapatra P, Swarnakar S. EGFR-mediated matrix metalloproteinase-7 up-regulation promotes epithelial-mesenchymal transition via ERK1-AP1 axis during ovarian endometriosis progression. FASEB J. 2018;32:4560–72. De Iaco P, Marabini A, Stefanetti M, Del Vecchio C, Bovicelli L. Acceptability and pain of outpatient hysteroscopy. J Am Assoc Gynecol Laparosc. 2000;7:71–5. Geiss GK, Bumgarner RE, Birditt B, Dahl T, Dowidar N, Dunaway DL, et al. Direct multiplexed measurement of gene expression with color-coded probe pairs. Nat Biotechnol. 2008;26:317–25. Ponnampalam AP, Weston GC, Trajstman AC, Susil B, Rogers PAW. Molecular classification of human endometrial cycle stages by transcriptional profiling. Mol Hum Reprod. 2004;10:879–93. Funding This study was funded by Centro de Desarrollo Tecnológico Industrial (grant IDI-2013039), Spain. The Industrial Doctorate Agency for Administration of University and Research Grants, Catalonia, Spain, also supported this work (DI2015_074). Funding agencies were not involved in the study design, collection of data, writing of the report, or decision to submit the article. Author information Authors and Affiliations Corresponding author Ethics declarations All samples were collected under an approved protocol after obtaining written informed consent. Use of uterine specimens was approved by the Ethics Committee of Vall d’Hebron Research Institute in Barcelona, Spain (PR(AMI)410/2016). Conflict of interest The authors declare that they have no conflict of interest. Additional information Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Electronic supplementary material Supplemental Figure 1 (download JPG ) Scatter plots of control patients. The graphs represent the number of copies detected in Nanostring per each gene in the control group. P Value (unpaired T-test) compares the expression of controls who underwent laparoscopy and who did not undergo the procedure. (JPG 104 kb). ESM 2 (download DOCX ) (DOCX 60 kb). ESM 3 (download DOCX ) (DOCX 13 kb). Rights and permissions About this article Cite this article Vallvé-Juanico, J., López-Gil, C., Ponomarenko, J. et al. External validation of putative biomarkers in eutopic endometrium of women with endometriosis using NanoString technology. J Assist Reprod Genet 37, 2981–2987 (2020). https://doi.org/10.1007/s10815-020-01965-6 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s10815-020-01965-6

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

Ask this paper AI returns verbatim quotes from the full text · source: oa-doi-fallback

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Condition tags

endometriosis

MeSH descriptors

Biomarkers Endometriosis Endometrium Nanotechnology Real-Time Polymerase Chain Reaction Adolescent Adult Biomarkers Case-Control Studies Endometriosis Endometriosis Endometriosis Endometrium Endometrium Female Humans Middle Aged Nanotechnology Real-Time Polymerase Chain Reaction Young Adult

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 (44)

Cited by (4)

Source provenance

europepmc
last seen: 2026-07-31T06:09:14.520117+00:00
openalex
last seen: 2026-06-10T17:14:06.276822+00:00
pubmed
last seen: 2026-05-13T22:21:42.008780+00:00
License: CC0 · commercial use OK