{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:36:07Z","timestamp":1785411367642,"version":"3.56.0"},"reference-count":49,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471683"],"award-info":[{"award-number":["82471683"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82471683"],"award-info":[{"award-number":["82471683"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2704000"],"award-info":[{"award-number":["2022YFC2704000"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: The diagnosis of endometriosis (EM) remains challenging due to the lack of a perfect diagnostic standard and the poor concordance between clinical symptoms and lesion severity. Although laparoscopy is widely used in clinical practice, it is invasive and associated with a non-negligible false-negative rate, while serum CA125 has limited diagnostic accuracy. In our previous studies, circulating endometrial cells (CECs) were identified in the peripheral blood of patients with EM, suggesting their potential as a non-invasive biomarker. Building on this finding, the present study aimed to systematically evaluate the clinical value of CECs in the diagnosis and stratified diagnosis of EM in the absence of a perfect diagnostic reference standard. Methods: Female patients treated at the Department of Obstetrics and Gynecology, Peking University People\u2019s Hospital, between June 2022 and June 2024 were enrolled. Participants were clinically classified according to laparoscopic evaluation into an EM group and a non-EM group. However, laparoscopy was not treated as a definitive diagnostic gold standard in the statistical analysis. Instead, given the absence of a perfect reference standard, nonparametric latent class analysis was applied to jointly estimate disease status and the diagnostic performance of CECs, CA125, and laparoscopy. Patients with EM were further stratified according to dysmenorrhea severity (mild, moderate, and severe), lesion activity status (active or dormant), and menstrual cycle phase. Peripheral blood samples were collected from all participants, and CECs were detected using subtraction enrichment combined with immunofluorescence and fluorescence in situ hybridization (SE-iFISH). Serum CA125 levels were measured concurrently. Results: A total of 302 participants were included. The primary analysis focused on 133 surgically confirmed EM patients and 146 non-EM controls. After adjustment for an imperfect diagnostic reference standard, CECs demonstrated superior diagnostic performance compared with serum CA125 in the overall cohort, with higher sensitivity (0.58 vs. 0.37) and specificity (0.81 vs. 0.75). Under laparoscopic assessment in patients with severe dysmenorrhea (VAS \u2265 7), where the sensitivity and specificity were 0.759 and 1.00, respectively, CECs demonstrated superior diagnostic performance compared with serum CA125, with higher sensitivity (0.694 vs. 0.355) and specificity (0.946 vs. 0.429). Similarly, in patients with active EM, where laparoscopy showed a sensitivity of 0.79 and a specificity of 1.00, CECs again demonstrated superior diagnostic performance compared with CA125 (sensitivity 0.73 vs. 0.35; specificity 0.96 vs. 0.31), showing high concordance with laparoscopic diagnosis. When stratified by menstrual cycle phase, CECs maintained superior diagnostic performance over CA125 during both the proliferative and menstrual phases, with higher sensitivity (0.84 vs. 0.44) and specificity (0.83 vs. 0.65). Conclusions: Circulating endometrial cells (CECs) demonstrate high diagnostic accuracy for EM, significantly outperforming serum CA125, and show high concordance with laparoscopic diagnosis across clinically relevant stratified conditions in the absence of a perfect diagnostic gold standard.<\/jats:p>","DOI":"10.3390\/jcm15083021","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T15:56:56Z","timestamp":1776268616000},"page":"3021","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Value of Circulating Endometrial Cells in the Diagnosis and Stratified Diagnosis of Endometriosis"],"prefix":"10.3390","volume":"15","author":[{"given":"Shang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Peking University People\u2019s Hospital, Beijing 100044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Buyun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Peking University People\u2019s Hospital, Beijing 100044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Peking University People\u2019s Hospital, Beijing 100044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianchen","family":"Tai","sequence":"additional","affiliation":[{"name":"School of Mathematical Sciences, Peking University, Beijing 100871, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Peking University People\u2019s Hospital, Beijing 100044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6613-8764","authenticated-orcid":false,"given":"Honglan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Peking University People\u2019s Hospital, Beijing 100044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiping","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Peking University People\u2019s Hospital, Beijing 100044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoting","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Peking University People\u2019s Hospital, Beijing 100044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Peking University People\u2019s Hospital, Beijing 100044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7935-1222","authenticated-orcid":false,"given":"Xiaohua","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Peking University, Beijing 100871, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Peking University People\u2019s Hospital, Beijing 100044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1001\/jama.2025.2975","article-title":"Endometriosis: A Review","volume":"334","author":"Mackenzie","year":"2025","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1097\/MS9.0000000000001592","article-title":"Spontaneous recurrent menstrual pneumothorax: A case report","volume":"86","author":"Hirono","year":"2024","journal-title":"Ann. 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