Identificación de Biomarcadores Precoces para el Diagnóstico de Endometriosis
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https://doi.org/10.56048/MQR20225.9.1.2025.e231Palabras clave:
Biomarcadores; Endometriosis; Diagnóstico; Disfunción; inmunológica; InflamaciónResumen
La endometriosis es una enfermedad ginecológica progresiva caracterizada por la migración de células endometriales fuera del útero, asociada con inflamación crónica y una patogénesis incierta. Este estudio tuvo como objetivo identificar biomarcadores precoces para el diagnóstico de la endometriosis mediante una revisión sistemática de la literatura científica. Siguiendo la metodología PRISMA, se formularon preguntas de investigación centradas en los aspectos inmunológicos y de angiogénesis, los biomarcadores más relevantes en estudio y los desafíos en su validación. Se realizó una búsqueda exhaustiva en bases de datos como Scopus, PubMed y Web of Science, abarcando publicaciones entre 2018 y 2024. Los resultados muestran que, aunque se han identificado numerosos biomarcadores potenciales, incluyendo glicoproteínas, citocinas inflamatorias, marcadores de estrés oxidativo, factores de crecimiento, autoanticuerpos, miRNAs y lncRNAs, ninguno ha alcanzado una sensibilidad y especificidad adecuadas para su uso clínico universal. La heterogeneidad de la enfermedad y la variabilidad en los estudios dificultan la implementación de un biomarcador único. No obstante, la combinación de múltiples biomarcadores podría mejorar la precisión diagnóstica. En conclusión, la identificación de biomarcadores precoces es esencial para desarrollar herramientas diagnósticas no invasivas y efectivas, transformando el manejo clínico de la endometriosis, reduciendo la necesidad de procedimientos invasivos y permitiendo intervenciones terapéuticas personalizada.
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Laganà AS, Garzon S, Götte M, Viganò P, Franchi M, Ghezzi F, et al. The Pathogenesis of Endometriosis: Molecular and Cell Biology Insights. Int J Mol Sci. 2019 Nov 10;20(22):5615.
de Fáveri C, Fermino PMP, Piovezan AP, Volpato LK. The Inflammatory Role of Pro-Resolving Mediators in Endometriosis: An Integrative Review. Int J Mol Sci. 2021 Apr 22;22(9):4370.
Kim H, Choi YS, Kim JS, Kim S, Won BH, Won Y Bin, et al. Identification of Serum Biomarkers for Diagnosis of Endometriosis Using Multiplex Immunoassays. Reproductive Sciences. 2020 May 6;27(5):1139–47.
Machairiotis N, Vasilakaki S, Thomakos N. Inflammatory Mediators and Pain in Endometriosis: A Systematic Review. Biomedicines. 2021 Jan 8;9(1):54.
Moga MA, Bălan A, Dimienescu OG, Burtea V, Dragomir RM, Anastasiu CV. Circulating miRNAs as Biomarkers for Endometriosis and Endometriosis-Related Ovarian Cancer—An Overview. J Clin Med. 2019 May 23;8(5):735.
Taylor HS, Kotlyar AM, Flores VA. Endometriosis is a chronic systemic disease: clinical challenges and novel innovations. The Lancet. 2021 Feb;397(10276):839–52.
Tian Z, Chang XH, Zhao Y, Zhu HL. Current biomarkers for the detection of endometriosis. Chin Med J (Engl). 2020 Oct 5;133(19):2346–52.
Samimi M, Pourhanifeh MH, Mehdizadehkashi A, Eftekhar T, Asemi Z. The role of inflammation, oxidative stress, angiogenesis, and apoptosis in the pathophysiology of endometriosis: Basic science and new insights based on gene expression. J Cell Physiol. 2019 Nov 19;234(11):19384–92.
Kimber-Trojnar Ż, Pilszyk A, Niebrzydowska M, Pilszyk Z, Ruszała M, Leszczyńska-Gorzelak B. The Potential of Non-Invasive Biomarkers for Early Diagnosis of Asymptomatic Patients with Endometriosis. J Clin Med. 2021 Jun 23;10(13):2762.
DeAngelo C, Tarasiewicz MB, Strother A, Taggart H, Gray C, Shanahan M, et al. Endometriosis: A Malignant Fingerprint. J Cancer Res Ther Oncol. 2020 Apr;8(2).
Sampson JA. Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol. 1927;14(4):422–69.
Yovich JL, Rowlands PK, Lingham S, Sillender M, Srinivasan S. Pathogenesis of endometriosis: Look no further than John Sampson. Reprod Biomed Online. 2020 Jan;40(1):7–11.
Zondervan KT, Becker CM, Missmer SA. Endometriosis. New England Journal of Medicine. 2020 Mar 26;382(13):1244–56.
Basta A, Brucka A, Górski J, Kotarski J, Kulig B, Oszukowski P, et al. The statement of Polish Society’s Experts Group concerning diagnostics and methods of endometriosis treatment. Ginekol Pol [Internet]. 2012 Nov;83(11):871—876. Available from: http://europepmc.org/abstract/MED/23379199
Brown J, Farquhar C. Endometriosis: an overview of Cochrane Reviews. Cochrane Database of Systematic Reviews. 2014 Mar 10;2014(8).
Falcone T, Flyckt-Rebecca R. Clinical management of endometriosis. Obstetrics and Gynecology. 2018;131(3):557–71.
He Y, Li J, Qu Y, Sun L, Zhao X, Wu H, et al. Identification and Analysis of Potential Immune-Related Biomarkers in Endometriosis. J Immunol Res. 2023 Jan 10;2023:1–21.
Kiesel L, Sourouni M. Diagnosis of endometriosis in the 21st century. Climacteric. 2019 May 4;22(3):296–302.
Pino I, Belloni GM, Barbera V, Solima E, Radice D, Angioni S, et al. “Better late than never but never late is better”, especially in young women. A multicenter Italian study on diagnostic delay for symptomatic endometriosis. The European Journal of Contraception & Reproductive Health Care. 2023 Jan 2;28(1):10–6.
Menakaya U, Reid S, Lu C, Gerges B, Infante F, Condous G. Performance of ultrasound-based endometriosis staging system (UBESS) for predicting level of complexity of laparoscopic surgery for endometriosis. Ultrasound Obstet Gynecol. 2016 Dec;48(6):786–95.
Bourdel N, Chauvet P, Billone V, Douridas G, Fauconnier A, Gerbaud L, et al. Systematic review of quality of life measures in patients with endometriosis. PLoS One. 2019 Jan 10;14(1):e0208464.
Irungu S, Mavrelos D, Worthington J, Blyuss O, Saridogan E, Timms JF. Discovery of non-invasive biomarkers for the diagnosis of endometriosis. Clin Proteomics. 2019 Dec 6;16(1):14.
Nisenblat V, Bossuyt PM, Shaikh R, Farquhar C, Jordan V, Scheffers CS, et al. Blood biomarkers for the non-invasive diagnosis of endometriosis. Cochrane Database of Systematic Reviews. 2016 May 1;2016(5).
American Society for Clinical Pharmacology & Therapeutics. Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001 Mar;69(3):89–95.
Luisi S, Pinzauti S, Regini C, Petraglia F. Serum Markers for the Noninvasive Diagnosis of Endometriosis. Women’s Health. 2015 Sep 12;11(5):603–10.
Coutinho LM, Ferreira MC, Rocha ALL, Carneiro MM, Reis FM. New biomarkers in endometriosis. In: Advances in Clinical Chemistry. 2019. p. 59–77.
Rogers PAW, D’Hooghe TM, Fazleabas A, Giudice LC, Montgomery GW, Petraglia F, et al. Defining Future Directions for Endometriosis Research: Workshop Report From the 2011 World Congress of Endometriosis in Montpellier, France. Reproductive Sciences. 2013 May 30;20(5):483–99.
O DF, Flores I, Waelkens E, D’Hooghe T. Noninvasive diagnosis of endometriosis: Review of current peripheral blood and endometrial biomarkers. Best Pract Res Clin Obstet Gynaecol. 2018 Jul;50:72–83.
Fassbender A, Burney RO, F. O D, D’Hooghe T, Giudice L. Update on Biomarkers for the Detection of Endometriosis. Biomed Res Int. 2015;2015:1–14.
Anastasiu CV, Moga MA, Elena Neculau A, Bălan A, Scârneciu I, Dragomir RM, et al. Biomarkers for the Noninvasive Diagnosis of Endometriosis: State of the Art and Future Perspectives. Int J Mol Sci. 2020 Mar 4;21(5):1750.
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021 Mar 29;n71.
Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015 Dec 1;4(1):1.
Lee SH, Sapkota Y, Fung J, Montgomery GW. Genetic Biomarkers for Endometriosis. In: Biomarkers for Endometriosis. Cham: Springer International Publishing; 2017. p. 83–93.
Shafrir AL, Farland LV, Shah DK, Harris HR, Kvaskoff M, Zondervan K, et al. Risk for and consequences of endometriosis: A critical epidemiologic review. Best Pract Res Clin Obstet Gynaecol. 2018 Aug;51:1–15.
Hudson QJ, Perricos A, Wenzl R, Yotova I. Challenges in uncovering non-invasive biomarkers of endometriosis. Exp Biol Med. 2020 Mar 4;245(5):437–47.
Izumi G, Koga K, Takamura M, Makabe T, Satake E, Takeuchi A, et al. Involvement of immune cells in the pathogenesis of endometriosis. Journal of Obstetrics and Gynaecology Research. 2018 Feb 5;44(2):191–8.
Fassbender A, O D, Becker CM, D’Hooghe T. Peripheral Blood Biomarkers for Endometriosis. In: Biomarkers for Endometriosis. Cham: Springer International Publishing; 2017. p. 123–39.
Barcena de Arellano ML, Arnold J, Vercellino GF, Chiantera V, Ebert AD, Schneider A, et al. Influence of Nerve Growth Factor in Endometriosis-Associated Symptoms. Reproductive Sciences. 2011 Dec 30;18(12):1202–10.
Chapron C, Marcellin L, Borghese B, Santulli P. Rethinking mechanisms, diagnosis and management of endometriosis. Nat Rev Endocrinol. 2019 Nov 5;15(11):666–82.
Bulun SE, Yilmaz BD, Sison C, Miyazaki K, Bernardi L, Liu S, et al. Endometriosis. Endocr Rev. 2019 Aug 1;40(4):1048–79.
Wang PH, Yang ST, Chang WH, Liu CH, Lee FK, Lee WL. Endometriosis: Part I. Basic concept. Taiwan J Obstet Gynecol. 2022 Nov;61(6):927–34.
Carrillo Torres P, Martínez Zamora MA, Carmona Herrera F. Endometriosis. Un largo camino. Clin Invest Ginecol Obstet. 2021 Oct;48(4):100686.
Koninckx PR, Fernandes R, Ussia A, Schindler L, Wattiez A, Al-Suwaidi S, et al. Pathogenesis Based Diagnosis and Treatment of Endometriosis. Front Endocrinol (Lausanne). 2021 Nov 25;12.
Hosseini M, Hammami B, Kazemi M. Identification of potential diagnostic biomarkers and therapeutic targets for endometriosis based on bioinformatics and machine learning analysis. J Assist Reprod Genet. 2023 Oct 9;40(10):2439–51.
Laganà AS, Salmeri FM, Ban Frangež H, Ghezzi F, Vrtačnik-Bokal E, Granese R. Evaluation of M1 and M2 macrophages in ovarian endometriomas from women affected by endometriosis at different stages of the disease. Gynecological Endocrinology. 2020 May 3;36(5):441–4.
Nie MF, Xie Q, Wu YH, He H, Zou LJ, She XL, et al. Serum and Ectopic Endometrium from Women with Endometriosis Modulate Macrophage M1/M2 Polarization via the Smad2/Smad3 Pathway. J Immunol Res. 2018 Sep 12;2018:1–14.
Moustafa S, Burn M, Mamillapalli R, Nematian S, Flores V, Taylor HS. Accurate diagnosis of endometriosis using serum microRNAs. Am J Obstet Gynecol. 2020 Oct;223(4):557.e1-557.e11.
Osuga Y, Hirota Y, Hirata T, Takamura M, Urata Y, Harada M, et al. Th2 Cells and Th17 Cells in the Development of Endometriosis – Possible Roles of Interleukin-4 and Interleukin-17A. J Endometr Pelvic Pain Disord. 2016 Oct 22;8(4):136–40.
He Y, Li J, Qu Y, Sun L, Zhao X, Wu H, et al. Identification and Analysis of Potential Immune-Related Biomarkers in Endometriosis. J Immunol Res. 2023 Jan 10;2023:1–21.
Ahn SH, Edwards AK, Singh SS, Young SL, Lessey BA, Tayade C. IL-17A Contributes to the Pathogenesis of Endometriosis by Triggering Proinflammatory Cytokines and Angiogenic Growth Factors. The Journal of Immunology. 2015 Sep 15;195(6):2591–600.
Machado DE, Rodrigues-Baptista KC, Alessandra-Perini J, Soares de Moura R, Santos TA dos, Pereira KG, et al. Euterpe oleracea Extract (Açaí) Is a Promising Novel Pharmacological Therapeutic Treatment for Experimental Endometriosis. PLoS One. 2016 Nov 16;11(11):e0166059.
Volpert O V., Fong T, Koch AE, Peterson JD, Waltenbaugh C, Tepper RI, et al. Inhibition of Angiogenesis by Interleukin 4. J Exp Med. 1998 Sep 21;188(6):1039–46.
Mihalyi A, Gevaert O, Kyama CM, Simsa P, Pochet N, De Smet F, et al. Non-invasive diagnosis of endometriosis based on a combined analysis of six plasma biomarkers. Human Reproduction. 2010 Mar 1;25(3):654–64.
Agic A, Djalali S, Wolfler MM, Halis G, Diedrich K, Hornung D. Combination of CCR1 mRNA, MCP1, and CA125 Measurements in Peripheral Blood as a Diagnostic Test for Endometriosis. Reproductive Sciences. 2008 Nov 30;15(9):906–11.
Mosbah A, Nabiel Y, Khashaba E. Interleukin‐6, intracellular adhesion molecule‐1, and glycodelin A levels in serum and peritoneal fluid as biomarkers for endometriosis. International Journal of Gynecology & Obstetrics. 2016 Sep 2;134(3):247–51.
Kocbek V, Vouk K, Bersinger NA, Mueller MD, Lanišnik Rižner T. Panels of Cytokines and Other Secretory Proteins as Potential Biomarkers of Ovarian Endometriosis. The Journal of Molecular Diagnostics. 2015 May;17(3):325–34.
Othman EEDR, Hornung D, Salem HT, Khalifa EA, El-Metwally TH, Al-Hendy A. Serum cytokines as biomarkers for nonsurgical prediction of endometriosis. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2008 Apr;137(2):240–6.
Borrelli GM, Abrao MS, Mechsner S. Can chemokines be used as biomarkers for endometriosis? A systematic review. Human Reproduction. 2014 Feb 1;29(2):253–66.
Martínez S, Garrido N, Coperias JL, Pardo F, Desco J, García-Velasco JA, et al. Serum interleukin-6 levels are elevated in women with minimal–mild endometriosis. Human Reproduction. 2007 Mar;22(3):836–42.
Socolov R, Butureanu S, Angioni S, Sindilar A, Boiculese L, Cozma L, et al. The value of serological markers in the diagnosis and prognosis of endometriosis: a prospective case–control study. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2011 Feb;154(2):215–7.
Kikuchi Y, Ishikawa N, Hirata U, Imaizumi E, Sasa H, Nagata I. Changes of peripheral blood lymphocyte subsets before and after operation of patients with endometriosis. Acta Obstet Gynecol Scand. 1993 Apr 7;72(3):157–61.
Li J, He Y, Liang T, Wang J, Jiang X, Zhang G. Identification of Potential Differentially Methylated Gene-Related Biomarkers in Endometriosis. Epigenomics. 2022 Oct 31;14(19):1157–79.
Scutiero G, Iannone P, Bernardi G, Bonaccorsi G, Spadaro S, Volta CA, et al. Oxidative Stress and Endometriosis: A Systematic Review of the Literature. Oxid Med Cell Longev. 2017;2017:1–7.
Ozhan E, Kokcu A, Yanik K, Gunaydin M. Investigation of diagnostic potentials of nine different biomarkers in endometriosis. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2014 Jul;178:128–33.
Yi Y, Wang S, Chao C, Su C, Lee Y, Chen L. Evaluation of serum autoantibody levels in the diagnosis of ovarian endometrioma. J Clin Lab Anal. 2010 Jan 20;24(5):357–62.
Gajbhiye R, Sonawani A, Khan S, Suryawanshi A, Kadam S, Warty N, et al. Identification and validation of novel serum markers for early diagnosis of endometriosis. Human Reproduction. 2012 Feb 1;27(2):408–17.
Vanhie A, O D, Peterse D, Beckers A, Cuéllar A, Fassbender A, et al. Plasma miRNAs as biomarkers for endometriosis. Human Reproduction. 2019 Sep 29;34(9):1650–60.
Bendifallah S, Suisse S, Puchar A, Delbos L, Poilblanc M, Descamps P, et al. Salivary MicroRNA Signature for Diagnosis of Endometriosis. J Clin Med. 2022 Jan 26;11(3):612.
Soltani-Fard E, Asadi M, Taghvimi S, Vafadar A, Vosough P, Tajbakhsh A, et al. Exosomal microRNAs and long noncoding RNAs: as novel biomarkers for endometriosis. Cell Tissue Res. 2023 Oct 22;394(1):55–74.
Tahermanesh K, Hakimpour S, Govahi A, Rokhgireh S, Mehdizadeh M, Minaeian S, et al. Evaluation of expression of biomarkers of PLAGL1 (ZAC1), microRNA, and their non-coding RNAs in patients with endometriosis. J Gynecol Obstet Hum Reprod. 2023 Apr;52(4):102568.
Pant A, Moar K, K. Arora T, Maurya PK. Biomarkers of endometriosis. Clinica Chimica Acta. 2023 Sep;549:117563.
Chen X, Liu H, Sun W, Guo Z, Lang J. Elevated urine histone 4 levels in women with ovarian endometriosis revealed by discovery and parallel reaction monitoring proteomics. J Proteomics. 2019 Jul;204:103398.
Proestling K, Wenzl R, Yotova I, Hauser C, Husslein H, Kuessel L. Investigating selected adhesion molecules as urinary biomarkers for diagnosing endometriosis. Reprod Biomed Online. 2020 Apr;40(4):555–8.
Bae SJ, Jo Y, Cho MK, Jin JS, Kim JY, Shim J, et al. Identification and analysis of novel endometriosis biomarkers via integrative bioinformatics. Front Endocrinol (Lausanne). 2022 Oct 20;13.
Ghasemi F, Alemzadeh E, Allahqoli L, Alemzadeh E, Mazidimoradi A, Salehiniya H, et al. MicroRNAs Dysregulation as Potential Biomarkers for Early Diagnosis of Endometriosis. Biomedicines. 2022 Oct 13;10(10):2558.
Moein Mahini S, Younesi M, Mortazavi G, Samare-Najaf M, Karim Azadbakht M, Jamali N. Non-invasive diagnosis of endometriosis: Immunologic and genetic markers. Clinica Chimica Acta. 2023 Jan;538:70–86.
Li J, Guan L, Zhang H, Gao Y, Sun J, Gong X, et al. Endometrium metabolomic profiling reveals potential biomarkers for diagnosis of endometriosis at minimal-mild stages. Reproductive Biology and Endocrinology. 2018 Dec 30;16(1):42.
Višnić A, Čanadi Jurešić G, Domitrović R, Klarić M, Šepić TS, Barišić D. Proteins in urine – Possible biomarkers of endometriosis. J Reprod Immunol. 2023 Jun;157:103941.
Janša V, Pušić Novak M, Ban Frangež H, Rižner TL. TGFBI as a candidate biomarker for non-invasive diagnosis of early-stage endometriosis. Human Reproduction. 2023 Jul 5;38(7):1284–96.
Ding H, Xu H, Zhang T, Shi C. Identification and validation of M2 macrophage-related genes in endometriosis. Heliyon. 2023 Nov;9(11):e22258.
Wang J, Cong S, Wu H, He Y, Liu X, Sun L, et al. Identification and Analysis of Potential Autophagy-Related Biomarkers in Endometriosis by WGCNA. Front Mol Biosci. 2021 Nov 1;8.
Herranz-Blanco B, Daoud E, Viganò P, García-Velasco JA, Colli E. Development and Validation of an Endometriosis Diagnostic Method Based on Serum Biomarkers and Clinical Variables. Biomolecules. 2023 Jun 28;13(7):1052.
Viganò P, Casalechi M, Dolmans MM. European Union underinvestment in endometriosis research. Journal of Endometriosis and Uterine Disorders. 2024 Mar;5:100058.
Li J, Gao Y, Guan L, Zhang H, Sun J, Gong X, et al. Discovery of Phosphatidic Acid, Phosphatidylcholine, and Phosphatidylserine as Biomarkers for Early Diagnosis of Endometriosis. Front Physiol. 2018 Jan 23;9.
Jiang H, Zhang X, Wu Y, Zhang B, Wei J, Li J, et al. Bioinformatics identification and validation of biomarkers and infiltrating immune cells in endometriosis. Front Immunol. 2022 Nov 29;13.
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