{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T16:02:06Z","timestamp":1792425726482,"version":"4.5.0"},"reference-count":26,"publisher":"Pensoft Publishers","issue":"1","license":[{"start":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T00:00:00Z","timestamp":1740441600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["FM"],"abstract":"<jats:p><jats:bold>Introduction<\/jats:bold>: Endometrial carcinoma (EC) is the most common gynecological cancer among women, and in more than 90% of cases, the initial manifestation of the disease is postmenopausal bleeding. Unfortunately, despite early diagnosis and treatment, EC often recurs. Among the many serum tumor markers studied, human epididymis protein 4 (HE4) and cancer antigen 125 (CA125) show the most promise as tools for EC diagnosis, prognosis, and monitoring.<\/jats:p>\n          <jats:p><jats:bold>Aim<\/jats:bold>: The aim of the current study was to evaluate the clinical usefulness of HE4 and CA125, tested either as single markers or in combination by including them in the Risk of Ovarian Malignancy Algorithms (ROMA) and in Copenhagen index (CPH-I).<\/jats:p>\n          <jats:p><jats:bold>Material and methods<\/jats:bold>: In this retrospective study, 1262 women (74 with confirmed EC) were included. The patients with EC had significantly higher values for HE4, CA125, ROMA, and CPH-I (<jats:italic>p<\/jats:italic>&amp;lt;0.001) than the healthy women and patients with benign diseases. The subgroup analysis based on the histological type of EC revealed that the highest markers and algorithms were recorded in type II EC group.<\/jats:p>\n          <jats:p><jats:bold>Results<\/jats:bold>: The ROC curve analysis showed that the best diagnostic performance for detecting EC among patients with benign diseases was the ROMA index (AUC=0.869; 95% CI: 0.818-0.920), followed by CPH-I (AUC=0.822; 95% CI: 0.757-0.887), and HE4 (AUC=0.816; 95% CI: 0.750-0.881). Tested alone, CA125 presented unsatisfactory results for this purpose. Both algorithms proved to have a correlation with the disease stage and progression better than the markers alone (HR=1.046 vs. HR=1.018).<\/jats:p>\n          <jats:p><jats:bold>Conclusion<\/jats:bold>: In summary, the ROMA index, CPH-I, and, to a lesser extent, standalone HE4 testing can supplement imaging methods as reliable tools for diagnosing and distinguishing patients with EC from those with benign conditions. They have potential as prognostic markers for advanced disease and could help gynecological oncologists to develop a therapeutic strategy.<\/jats:p>","DOI":"10.3897\/folmed.67.e143849","type":"journal-article","created":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T14:00:24Z","timestamp":1740492024000},"source":"Crossref","is-referenced-by-count":3,"title":["Clinical significance of human epididymis protein 4 (HE4), cancer antigen 125 (CA125), the risk of ovarian malignancy algorithm (ROMA), and Copenhagen index (CPH-I) for the diagnosis of endometrial carcinoma"],"prefix":"10.3897","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9900-708X","authenticated-orcid":true,"given":"Vesselina","family":"Koleva","sequence":"first","affiliation":[{"name":"Tokuda University Hospital, Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sevim","family":"Shefket","sequence":"additional","affiliation":[{"name":"Prof. Dr Paraskev Stoyanov Medical University, Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Snezhana","family":"Stoencheva","sequence":"additional","affiliation":[{"name":"Medical University of Plovdiv, Plovdiv, Bulgaria"},{"name":"St. George University Hospital, Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2258","published-online":{"date-parts":[[2025,2,25]]},"reference":[{"key":"143849_B1","unstructured":"1. Uterine Cancer Statistics. Available from: https:\/\/www.wcrf.org\/preventing-cancer\/cancer-statistics\/endometrial-cancer-statistics\/(accessed on 07 January 2025)."},{"key":"143849_B2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1408"},{"key":"143849_B3","doi-asserted-by":"crossref","unstructured":"3. Crosbie E, Morrison J. The emerging epidemic of endometrial cancer: Time to take action. Cochrane Database Syst Rev 2014; 12:ED000095.","DOI":"10.1002\/14651858.ED000095"},{"key":"143849_B4","doi-asserted-by":"crossref","unstructured":"4. Clarke MA, Long BJ, Morillo ADM, et al. Association of endometrial cancer risk with postmenopausal bleeding in women. JAMA Intern Med 2018; 178:1210\u201322.","DOI":"10.1001\/jamainternmed.2018.2820"},{"key":"143849_B5","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23063412"},{"key":"143849_B6","doi-asserted-by":"crossref","unstructured":"6. Jones ER, O\u2019Flynn H, Njoku K, et al. Detecting endometrial cancer. Obstet Gynaecol 2021; 23:103\u201312.","DOI":"10.1111\/tog.12722"},{"key":"143849_B7","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-020-03007-z"},{"key":"143849_B8","doi-asserted-by":"crossref","unstructured":"8. Kirchhoff C, Habben I, Ivell R, et al. A major human epididymis-specific cDNA encodes a protein with sequence homology to extracellular proteinase inhibitors. Biol Reprod 1991; 45:350\u20137.","DOI":"10.1095\/biolreprod45.2.350"},{"key":"143849_B9","doi-asserted-by":"crossref","unstructured":"9. Li J, Chen H, Mariani A, et al. HE4 (WFDC2) promotes tumor growth in endometrial cancer cell lines. Int J Mol Sci 2013; 14:6026.","DOI":"10.3390\/ijms14036026"},{"key":"143849_B10","doi-asserted-by":"crossref","unstructured":"10. Lu Q, Chen H, Senkowski C, et al. Recombinant HE4 protein promotes proliferation of pancreatic and endometrial cancer cell lines. Oncol Rep 2015; 35:163\u201370.","DOI":"10.3892\/or.2015.4339"},{"key":"143849_B11","doi-asserted-by":"crossref","unstructured":"11. Degez M, Caillon H, Chauvir\u00e9-Drouard A, et al. Endometrial cancer: A systematic review of HE4, REM and REM-B. Clin Chim Acta 2021; 515:27\u201336.","DOI":"10.1016\/j.cca.2020.12.029"},{"key":"143849_B12","doi-asserted-by":"crossref","unstructured":"12. Li L-M, Zhu Y, Zhong Y, et al. Human epididymis protein 4 in endometrial cancer: A meta-analysis. Clin Chim Acta 2018; 482:215\u201323.","DOI":"10.1016\/j.cca.2018.03.040"},{"key":"143849_B13","doi-asserted-by":"crossref","unstructured":"13. Liu J, Han L, Sun Q, et al. Meta-analysis of the diagnostic accuracy of HE4 for endometrial carcinoma. Eur J Obstet Gynecol Reprod Biol 2020; 252:404\u201311.","DOI":"10.1016\/j.ejogrb.2020.07.015"},{"key":"143849_B14","doi-asserted-by":"crossref","unstructured":"14. Li J, Wang X, Qu W, et al. Comparison of serum human epididymis protein 4 and CA125 on endometrial cancer detection: A meta-analysis. Clin Chim Acta 2019; 488:215\u201320.","DOI":"10.1016\/j.cca.2018.11.011"},{"key":"143849_B15","doi-asserted-by":"publisher","DOI":"10.21037\/tcr-20-2068"},{"key":"143849_B16","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics12112834"},{"key":"143849_B17","doi-asserted-by":"crossref","unstructured":"17. Karlsen MA, Hogdall EV, Christensen IJ, et al. A novel diagnostic index combining HE4, CA125 and age may improve triage of women with suspected ovarian cancer \u2013 an international multicenter study in women with ovarian mass. Gynecol Oncol 2015; 138:640\u20136.","DOI":"10.1016\/j.ygyno.2015.06.021"},{"key":"143849_B18","doi-asserted-by":"publisher","DOI":"10.1186\/s13048-019-0503-7"},{"key":"143849_B19","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231912041"},{"key":"143849_B20","doi-asserted-by":"publisher","DOI":"10.1080\/14737140.2017.1266263"},{"key":"143849_B21","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13194764"},{"key":"143849_B22","doi-asserted-by":"publisher","DOI":"10.3389\/fsurg.2022.1068492"},{"key":"143849_B23","doi-asserted-by":"crossref","unstructured":"23. Sun Y, Liu X, Zhao F, et al. Value of detection of serum human epididymis secretory protein 4 and carbohydrate antigen 125 in diagnosis of early endometrial cancer of different pathological subtypes. 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