{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T16:04:11Z","timestamp":1772640251035,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T00:00:00Z","timestamp":1628640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002261","name":"Russian Foundation for Basic Research","doi-asserted-by":"publisher","award":["19-315-90011"],"award-info":[{"award-number":["19-315-90011"]}],"id":[{"id":"10.13039\/501100002261","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Stem properties allow circulating tumor cells (CTCs) to survive in the bloodstream and initiate cancer progression. We aimed to assess the numbers of stem-like CTCs in patients with ovarian cancer (OC) before treatment and during first-line chemotherapy (CT). Flow cytometry was performed (Cytoflex S (Beckman Coulter, CA, USA)) using antibodies against CD45; epithelial markers EpCAM and cytokeratin (CK) 8,18; mesenchymal vimentin (vim); and stem-like CD44, CD133 and ALDH. This study included 38 stage I\u2013IV OC patients (median age 66 (Q1\u2013Q3 53\u201370)). The CK+vim- counts were higher (p = 0.012) and the CD133+ALDHhigh counts were lower (p = 0.010) before treatment in the neoadjuvant CT group than in the adjuvant group. The patients with ascites had more CK+vim- cells before treatment (p = 0.009) and less EpCAM-vim+ cells during treatment (p = 0.018) than the patients without ascites. All the CTC counts did not differ significantly in paired samples. Correlations were found between the CK-vim+ and CD133+ALDHhigh (r = 0.505, p = 0.027) and EpCAM-vim+ and ALDHhigh (r = 0.597, p = 0.004) cells before but not during treatment. Multivariate Cox regression analysis showed that progression-free survival was longer with the presence of surgical treatment (HR 0.06 95% CI 0.01\u20130.48, p = 0.009) and fewer CD133+ALDHveryhigh cells (HR 1.06 95% CI 1.02\u20131.12, p = 0.010). Thus, CD133+ALDH+ CTCs have the greatest prognostic potential in OC among the phenotypes studied.<\/jats:p>","DOI":"10.3390\/life11080815","type":"journal-article","created":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T04:56:22Z","timestamp":1628657782000},"page":"815","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Detection of Stem-Like Circulating Tumor Cells Could Increase the Clinical Applicability of Liquid Biopsy in Ovarian Cancer"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6970-6659","authenticated-orcid":false,"given":"Snezhanna O.","family":"Gening","sequence":"first","affiliation":[{"name":"Department of Human Physiology and Pathophysiology, Ulyanovsk State University, 42 Leo Tolstoy St., 432017 Ulyanovsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatyana V.","family":"Abakumova","sequence":"additional","affiliation":[{"name":"Department of Human Physiology and Pathophysiology, Ulyanovsk State University, 42 Leo Tolstoy St., 432017 Ulyanovsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dina U.","family":"Gafurbaeva","sequence":"additional","affiliation":[{"name":"OpenLab \u2018Gene and Cell Technologies\u2019, Kazan (Volga Region) Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9427-5739","authenticated-orcid":false,"given":"Albert A.","family":"Rizvanov","sequence":"additional","affiliation":[{"name":"OpenLab \u2018Gene and Cell Technologies\u2019, Kazan (Volga Region) Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inna I.","family":"Antoneeva","sequence":"additional","affiliation":[{"name":"Ulyanovsk Regional Clinical Oncology Center, 90 12th September St., 432048 Ulyanovsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6686-1968","authenticated-orcid":false,"given":"Regina R.","family":"Miftakhova","sequence":"additional","affiliation":[{"name":"OpenLab \u2018Gene and Cell Technologies\u2019, Kazan (Volga Region) Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrey B.","family":"Peskov","sequence":"additional","affiliation":[{"name":"Department of Human Physiology and Pathophysiology, Ulyanovsk State University, 42 Leo Tolstoy St., 432017 Ulyanovsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatyana P.","family":"Gening","sequence":"additional","affiliation":[{"name":"Department of Human Physiology and Pathophysiology, Ulyanovsk State University, 42 Leo Tolstoy St., 432017 Ulyanovsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1016\/S1470-2045(19)30456-5","article-title":"Progress in Cancer Survival, Mortality, and Incidence in Seven High-Income Countries 1995\u20132014 (ICBP SURVMARK-2): A Population-Based Study","volume":"20","author":"Arnold","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Schwarz, R.F., Ng, C.K.Y., Cooke, S.L., Newman, S., Temple, J., Piskorz, A.M., Gale, D., Sayal, K., Murtaza, M., and Baldwin, P.J. (2015). Spatial and Temporal Heterogeneity in High-Grade Serous Ovarian Cancer: A Phylogenetic Analysis. PLoS Med., 12.","DOI":"10.1371\/journal.pmed.1001789"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.ejca.2019.05.029","article-title":"Development and Validation of a Prognostic Nomogram for Overall Survival in Patients with Platinum-Resistant Ovarian Cancer Treated with Chemotherapy","volume":"117","author":"Lee","year":"2019","journal-title":"Eur. J. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/bjc.2013.717","article-title":"External Validation of Three Prognostic Models for Overall Survival in Patients with Advanced-Stage Epithelial Ovarian Cancer","volume":"110","author":"IntHout","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"100816","DOI":"10.1016\/j.mam.2019.07.008","article-title":"Circulating Tumor Cell as the Functional Aspect of Liquid Biopsy to Understand the Metastatic Cascade in Solid Cancer","volume":"72","year":"2020","journal-title":"Mol. Asp. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/s41419-019-1795-7","article-title":"Self-Seeding Circulating Tumor Cells Promote the Proliferation and Metastasis of Human Osteosarcoma by Upregulating Interleukin-8","volume":"10","author":"Liu","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.ccr.2014.05.002","article-title":"Hematogenous Metastasis of Ovarian Cancer: Rethinking Mode of Spread","volume":"26","author":"Pradeep","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4580","DOI":"10.7150\/thno.34337","article-title":"Circulating Tumor Cells as a Tool for Assessing Tumor Heterogeneity","volume":"9","author":"Heymann","year":"2019","journal-title":"Theranostics"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Yang, C., Zou, K., Zheng, L., and Xiong, B. (2017). Prognostic and Clinicopathological Significance of Circulating Tumor Cells Detected by RT-PCR in Non-Metastatic Colorectal Cancer: A Meta-Analysis and Systematic Review. BMC Cancer, 17.","DOI":"10.1186\/s12885-017-3704-8"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1007\/s12094-015-1372-1","article-title":"Prognostic Value of Circulating Tumor Cells in Metastatic Breast Cancer: A Systemic Review and Meta-Analysis","volume":"18","author":"Lv","year":"2016","journal-title":"Clin. Transl. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.ygyno.2015.03.002","article-title":"Treatment Monitoring of Patients with Epithelial Ovarian Cancer Using Invasive Circulating Tumor Cells (ICTCs)","volume":"137","author":"Pearl","year":"2015","journal-title":"Gynecol. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Loh, C.-Y., Chai, J., Tang, T., Wong, W., Sethi, G., Shanmugam, M., Chong, P., and Looi, C. (2019). The E-Cadherin and N-Cadherin Switch in Epithelial-to-Mesenchymal Transition: Signaling, Therapeutic Implications, and Challenges. Cells, 8.","DOI":"10.3390\/cells8101118"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Teeuwssen, M., and Fodde, R. (2019). Wnt Signaling in Ovarian Cancer Stemness, EMT, and Therapy Resistance. J. Clin. Med., 8.","DOI":"10.3390\/jcm8101658"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2796","DOI":"10.1002\/1878-0261.12762","article-title":"Epithelial\/Mesenchymal Heterogeneity of High-grade Serous Ovarian Carcinoma Samples Correlates with MiRNA Let-7 Levels and Predicts Tumor Growth and Metastasis","volume":"14","author":"Chirshev","year":"2020","journal-title":"Mol. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Tripathi, S., Jolly, M.K., Woodward, W.A., Levine, H., and Deem, M.W. (2018). Analysis of Hierarchical Organization in Gene Expression Networks Reveals Underlying Principles of Collective Tumor Cell Dissemination and Metastatic Aggressiveness of Inflammatory Breast Cancer. Front. Oncol., 8.","DOI":"10.3389\/fonc.2018.00244"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Yang, W., Kim, D., Kim, D.K., Choi, K.U., Suh, D.S., and Kim, J.H. (2021). Therapeutic Strategies for Targeting Ovarian Cancer Stem Cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22105059"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Lei, M.M.L., and Lee, T.K.W. (2021). Cancer Stem Cells: Emerging Key Players in Immune Evasion of Cancers. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.692940"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Liao, M., Wang, C., Yang, B., Huang, D., Zheng, Y., Wang, S., Wang, X., Zhang, J., Tang, C., and Xu, Z. (2021). Autophagy Blockade by Ai Du Qing Formula Promotes Chemosensitivity of Breast Cancer Stem Cells Via GRP78\/\u03b2-Catenin\/ABCG2 Axis. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.659297"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1111\/cas.14285","article-title":"Cancer Stem-like Cells with Hybrid Epithelial\/Mesenchymal Phenotype Leading the Collective Invasion","volume":"111","author":"Quan","year":"2020","journal-title":"Cancer Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1016\/j.molonc.2016.04.002","article-title":"Gene Expression Profiling of Single Circulating Tumor Cells in Ovarian Cancer\u2014Establishment of a Multi-Marker Gene Panel","volume":"10","author":"Blassl","year":"2016","journal-title":"Mol. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"48","DOI":"10.5114\/wo.2018.73885","article-title":"Surface Markers of Cancer Stem-like Cells of Ovarian Cancer and Their Clinical Relevance","volume":"2018","author":"Klemba","year":"2018","journal-title":"Wsp\u00f3\u0142czesna Onkol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Heong, V., Topp, M., Ananda, S., McNally, O., Lindeman, G.J., Haluska, P., Wakefield, M., Swisher, E.M., Tan, D.S., and Ruby, H. (2015). Targeting the C5 Subclass of High-Grade Serous Ovarian Cancer Using Patient-Derived Xenografts: Microtubule Polymerisation Inhibitors. J. Clin. Oncol., 33.","DOI":"10.1200\/jco.2015.33.15_suppl.e22202"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1007\/s10585-016-9821-y","article-title":"Mesothelial Cells Interact with Tumor Cells for the Formation of Ovarian Cancer Multicellular Spheroids in Peritoneal Effusions","volume":"33","author":"Matte","year":"2016","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1097\/IGC.0b013e31821bb8aa","article-title":"Clinical Trials in Recurrent Ovarian Cancer","volume":"21","author":"Friedlander","year":"2011","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/S1470-2045(15)00086-8","article-title":"Standard Chemotherapy with or without Bevacizumab for Women with Newly Diagnosed Ovarian Cancer (ICON7): Overall Survival Results of a Phase 3 Randomised Trial","volume":"16","author":"Oza","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"281","DOI":"10.3892\/ol.2016.5432","article-title":"Circulating Tumor Cells Expressing Cancer Stem Cell Marker CD44 as a Diagnostic Biomarker in Patients with Gastric Cancer","volume":"13","author":"Watanabe","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/j.ygyno.2011.05.028","article-title":"Circulating Tumor Cells Predict Progression Free Survival and Overall Survival in Patients with Relapsed\/Recurrent Advanced Ovarian Cancer","volume":"122","author":"Poveda","year":"2011","journal-title":"Gynecol. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.ygyno.2011.06.022","article-title":"Phase II Trial of the MTOR Inhibitor, Temsirolimus and Evaluation of Circulating Tumor Cells and Tumor Biomarkers in Persistent and Recurrent Epithelial Ovarian and Primary Peritoneal Malignancies: A Gynecologic Oncology Group Study","volume":"123","author":"Behbakht","year":"2011","journal-title":"Gynecol. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1007\/s00404-020-05477-7","article-title":"Clinical Relevance of Circulating Tumor Cells in Ovarian, Fallopian Tube and Peritoneal Cancer","volume":"301","author":"Fehm","year":"2020","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Obermayr, E., Reiner, A., Brandt, B., Braicu, E.I., Reinthaller, A., Loverix, L., Concin, N., Woelber, L., Mahner, S., and Sehouli, J. (2021). The Long-Term Prognostic Significance of Circulating Tumor Cells in Ovarian Cancer\u2014A Study of the OVCAD Consortium. Cancers, 13.","DOI":"10.3390\/cancers13112613"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"184945441878261","DOI":"10.1177\/1849454418782617","article-title":"Improved Ovarian Cancer EMT-CTC Isolation by Immunomagnetic Targeting of Epithelial EpCAM and Mesenchymal N-Cadherin","volume":"7","author":"Po","year":"2018","journal-title":"J. Circ. Biomark."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Gao, Y., Fan, W.-H., Song, Z., Lou, H., and Kang, X. (2021). Comparison of Circulating Tumor Cell (CTC) Detection Rates with Epithelial Cell Adhesion Molecule (EpCAM) and Cell Surface Vimentin (CSV) Antibodies in Different Solid Tumors: A Retrospective Study. PeerJ, 9.","DOI":"10.7717\/peerj.10777"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/978-3-030-14366-4_12","article-title":"Ovarian Cancer Stem Cell Heterogeneity","volume":"Volume 1139","author":"Birbrair","year":"2019","journal-title":"Stem Cells Heterogeneity in Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"158","DOI":"10.4161\/cc.8.1.7533","article-title":"Molecular Phenotyping of Human Ovarian Cancer Stem Cells Unravels the Mechanisms for Repair and Chemoresistance","volume":"8","author":"Alvero","year":"2009","journal-title":"Cell Cycle"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"91","DOI":"10.21037\/atm.2019.01.28","article-title":"Co-Expression of CD44\/MyD88 Is a Poor Prognostic Factor in Advanced Epithelial Ovarian Cancer","volume":"7","author":"Zhu","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Loreth, D., Schuette, M., Zinke, J., Mohme, M., Piffko, A., Schneegans, S., Stadler, J., Janning, M., Loges, S., and Joosse, S.A. (2021). CD74 and CD44 Expression on CTCs in Cancer Patients with Brain Metastasis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22136993"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Roy, L., Bobbs, A., Sattler, R., Kurkewich, J.L., Dausinas, P.B., Nallathamby, P., and Cowden Dahl, K.D. (2018). CD133 Promotes Adhesion to the Ovarian Cancer Metastatic Niche. Cancer Growth Metastasis, 11.","DOI":"10.1177\/1179064418767882"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1038\/modpathol.2011.170","article-title":"CD133 Expression Associated with Poor Prognosis in Ovarian Cancer","volume":"25","author":"Zhang","year":"2012","journal-title":"Mod. Pathol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1111\/j.1525-1438.2007.01056.x","article-title":"Expression of CD133-1 and CD133-2 in Ovarian Cancer","volume":"18","author":"Ferrandina","year":"2008","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1002\/ijc.25967","article-title":"Expression of Aldehyde Dehydrogenase and CD133 Defines Ovarian Cancer Stem Cells","volume":"130","author":"Kryczek","year":"2012","journal-title":"Int. J. Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.ygyno.2018.05.006","article-title":"The Prognostic Impact of Cancer Stem-like Cell Biomarker Aldehyde Dehydrogenase-1 (ALDH1) in Ovarian Cancer: A Meta-Analysis","volume":"150","author":"Ruscito","year":"2018","journal-title":"Gynecol. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3061","DOI":"10.1016\/j.celrep.2019.02.032","article-title":"A Pan-ALDH1A Inhibitor Induces Necroptosis in Ovarian Cancer Stem-like Cells","volume":"26","author":"Chefetz","year":"2019","journal-title":"Cell Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3991","DOI":"10.1158\/0008-5472.CAN-10-3175","article-title":"Aldehyde Dehydrogenase in Combination with CD133 Defines Angiogenic Ovarian Cancer Stem Cells That Portend Poor Patient Survival","volume":"71","author":"Silva","year":"2011","journal-title":"Cancer Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Meng, E., Mitra, A., Tripathi, K., Finan, M.A., Scalici, J., McClellan, S., da Silva, L.M., Reed, E., Shevde, L.A., and Palle, K. (2014). ALDH1A1 Maintains Ovarian Cancer Stem Cell-Like Properties by Altered Regulation of Cell Cycle Checkpoint and DNA Repair Network Signaling. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0107142"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.freeradbiomed.2012.11.010","article-title":"Aldehyde Dehydrogenases in Cellular Responses to Oxidative\/Electrophilicstress","volume":"56","author":"Singh","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Casagrande, N., Borghese, C., Agostini, F., Durante, C., Mazzucato, M., Colombatti, A., and Aldinucci, D. (2021). In Ovarian Cancer Multicellular Spheroids, Platelet Releasate Promotes Growth, Expansion of ALDH+ and CD133+ Cancer Stem Cells, and Protection against the Cytotoxic Effects of Cisplatin, Carboplatin and Paclitaxel. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22063019"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/11\/8\/815\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:43:57Z","timestamp":1760165037000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/11\/8\/815"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,11]]},"references-count":46,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["life11080815"],"URL":"https:\/\/doi.org\/10.3390\/life11080815","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,11]]}}}