Dynamic Monitoring of CD200 Mediated by Ascites-Derived Exosomes as a Predictor of Survival and Response to Front-Line Chemotherapeutics in Advanced High-Grade Serous Ovarian Cancer

Background: Exosomes, harboring donor-cell-derived biomarkers, are implicated in transferring oncologic protein and genetic materials. CD200, an immune checkpoint, has been engineered to affect immunosuppression in ovarian cancer. However, the potential of CD200 to serve as a predictor of ovarian ca...

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Main Authors: Ying Ji, Shanshan Liu, Genju Wang, Xin Chen, Yujuan Li, Xiaogai Zhi, Hongxiu Jiang, Juan Tang, Yi Ding, Shuli Zhao, Hongmei Zhou, Aiwei Xiong
Format: Article
Language:English
Published: IMR Press 2023-10-01
Series:Clinical and Experimental Obstetrics & Gynecology
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Online Access:https://www.imrpress.com/journal/CEOG/50/10/10.31083/j.ceog5010217
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author Ying Ji
Shanshan Liu
Genju Wang
Xin Chen
Yujuan Li
Xiaogai Zhi
Hongxiu Jiang
Juan Tang
Yi Ding
Shuli Zhao
Hongmei Zhou
Aiwei Xiong
author_facet Ying Ji
Shanshan Liu
Genju Wang
Xin Chen
Yujuan Li
Xiaogai Zhi
Hongxiu Jiang
Juan Tang
Yi Ding
Shuli Zhao
Hongmei Zhou
Aiwei Xiong
author_sort Ying Ji
collection DOAJ
description Background: Exosomes, harboring donor-cell-derived biomarkers, are implicated in transferring oncologic protein and genetic materials. CD200, an immune checkpoint, has been engineered to affect immunosuppression in ovarian cancer. However, the potential of CD200 to serve as a predictor of ovarian cancers remains unexplored. Methods: We performed dynamic measurements of exosome-mediated or serum CD200 levels at primary diagnosis, post-operation, and three cycles after chemotherapy. The receiver operating characteristic curve and cumulative survival rate were paralleled to decode the predictive and prognostic profiles. Results: Independent enrichment and identification of exosomes revealed a significant concentration of CD200, predominantly located within these exosomes. The CD200 level was elevated in non-responders compared to responders at the serial points and significantly decreased after treatment. At the 335.50 pg/mL cut-off, CD200 at primary diagnosis enabled accurate discrimination between responders and non-responders with an area under the curve (AUC) of 0.94 (95% confidence interval (CI) = 0.902–0.979, p = 0.01). With the cut-off dropping from 311.00 pg/mL to 265.00 pg/mL, the AUC decreased from 0.918 (95% CI = 0.873–0.963, p = 0.02) to 0.908 (95% CI = 0.862–0.955, p = 0.02), respectively. Elevated levels of CD200 levels at both primary diagnosis and three cycles after chemotherapy were identified as independent predictors for poor progression-free survival (PFS) (hazard ratio (HR) = 2.8, 95% CI = 2.08–3.49, p = 0.01; HR = 6.7, 95% CI = 4.01–8.02, p = 0.01, respectively) and overall survival (OS) (HR = 3.5, 95% CI = 2.14–4.99, p = 0.04; HR = 5.6, 95% CI = 3.01–7.34, p = 0.01, respectively). Based on CD200 dynamics, patients were stratified into high- and low-AUC groups. High CD200-AUC was independently associated with unfavourable PFS and OS (HR = 4.6, 95% CI = 3.6–15.7, p = 0.01; HR = 3.2, 95% CI = 1.5–6.3, p = 0.01, respectively). Conclusions: This study proposes high exosome-mediated CD200 as a liquid-based biomarker indicative of chemotolerance and dismal survival in ovarian neoplasms.
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spelling doaj-art-e1a689d116914195a54ca36340df8a3c2025-08-20T03:20:59ZengIMR PressClinical and Experimental Obstetrics & Gynecology0390-66632023-10-01501021710.31083/j.ceog5010217S0390-6663(23)02126-7Dynamic Monitoring of CD200 Mediated by Ascites-Derived Exosomes as a Predictor of Survival and Response to Front-Line Chemotherapeutics in Advanced High-Grade Serous Ovarian CancerYing Ji0Shanshan Liu1Genju Wang2Xin Chen3Yujuan Li4Xiaogai Zhi5Hongxiu Jiang6Juan Tang7Yi Ding8Shuli Zhao9Hongmei Zhou10Aiwei Xiong11Department of Gynecology and Obstetrics, the Second Hospital of Nanjing, Nanjing University of Chinese Medicine, 210003 Nanjing, Jiangsu, ChinaDepartment of Gynecology and Obstetrics, the Second Hospital of Nanjing, Nanjing University of Chinese Medicine, 210003 Nanjing, Jiangsu, ChinaDepartment of Gynecology and Obstetrics, the Second Hospital of Nanjing, Nanjing University of Chinese Medicine, 210003 Nanjing, Jiangsu, ChinaDepartment of Gynecology and Obstetrics, the Second Hospital of Nanjing, Nanjing University of Chinese Medicine, 210003 Nanjing, Jiangsu, ChinaDepartment of Gynecology and Obstetrics, Nanjing First Hospital, Nanjing Medical University, 210006 Nanjing, Jiangsu, ChinaDepartment of Gynecology and Obstetrics, Nanjing Maternal and Child Health Care Hospital, Nanjing Medical University, 210011 Nanjing, Jiangsu, ChinaDepartment of Gynecology and Obstetrics, the Second Hospital of Nanjing, Nanjing University of Chinese Medicine, 210003 Nanjing, Jiangsu, ChinaDepartment of Gynecology and Obstetrics, the Second Hospital of Nanjing, Nanjing University of Chinese Medicine, 210003 Nanjing, Jiangsu, ChinaDepartment of Gynecology and Obstetrics, the Second Hospital of Nanjing, Nanjing University of Chinese Medicine, 210003 Nanjing, Jiangsu, ChinaDepartment of the Central Lab, Nanjing First Hospital, Nanjing Medical University, 210006 Nanjing, Jiangsu, ChinaDepartment of Gynecology and Obstetrics, Nanjing Jiangning Hospital, Nanjing Medical University, 211100 Nanjing, Jiangsu, ChinaDepartment of Gynecology and Obstetrics, the Second Hospital of Nanjing, Nanjing University of Chinese Medicine, 210003 Nanjing, Jiangsu, ChinaBackground: Exosomes, harboring donor-cell-derived biomarkers, are implicated in transferring oncologic protein and genetic materials. CD200, an immune checkpoint, has been engineered to affect immunosuppression in ovarian cancer. However, the potential of CD200 to serve as a predictor of ovarian cancers remains unexplored. Methods: We performed dynamic measurements of exosome-mediated or serum CD200 levels at primary diagnosis, post-operation, and three cycles after chemotherapy. The receiver operating characteristic curve and cumulative survival rate were paralleled to decode the predictive and prognostic profiles. Results: Independent enrichment and identification of exosomes revealed a significant concentration of CD200, predominantly located within these exosomes. The CD200 level was elevated in non-responders compared to responders at the serial points and significantly decreased after treatment. At the 335.50 pg/mL cut-off, CD200 at primary diagnosis enabled accurate discrimination between responders and non-responders with an area under the curve (AUC) of 0.94 (95% confidence interval (CI) = 0.902–0.979, p = 0.01). With the cut-off dropping from 311.00 pg/mL to 265.00 pg/mL, the AUC decreased from 0.918 (95% CI = 0.873–0.963, p = 0.02) to 0.908 (95% CI = 0.862–0.955, p = 0.02), respectively. Elevated levels of CD200 levels at both primary diagnosis and three cycles after chemotherapy were identified as independent predictors for poor progression-free survival (PFS) (hazard ratio (HR) = 2.8, 95% CI = 2.08–3.49, p = 0.01; HR = 6.7, 95% CI = 4.01–8.02, p = 0.01, respectively) and overall survival (OS) (HR = 3.5, 95% CI = 2.14–4.99, p = 0.04; HR = 5.6, 95% CI = 3.01–7.34, p = 0.01, respectively). Based on CD200 dynamics, patients were stratified into high- and low-AUC groups. High CD200-AUC was independently associated with unfavourable PFS and OS (HR = 4.6, 95% CI = 3.6–15.7, p = 0.01; HR = 3.2, 95% CI = 1.5–6.3, p = 0.01, respectively). Conclusions: This study proposes high exosome-mediated CD200 as a liquid-based biomarker indicative of chemotolerance and dismal survival in ovarian neoplasms.https://www.imrpress.com/journal/CEOG/50/10/10.31083/j.ceog5010217exosomeovarian cancercd200prognosisresponse
spellingShingle Ying Ji
Shanshan Liu
Genju Wang
Xin Chen
Yujuan Li
Xiaogai Zhi
Hongxiu Jiang
Juan Tang
Yi Ding
Shuli Zhao
Hongmei Zhou
Aiwei Xiong
Dynamic Monitoring of CD200 Mediated by Ascites-Derived Exosomes as a Predictor of Survival and Response to Front-Line Chemotherapeutics in Advanced High-Grade Serous Ovarian Cancer
Clinical and Experimental Obstetrics & Gynecology
exosome
ovarian cancer
cd200
prognosis
response
title Dynamic Monitoring of CD200 Mediated by Ascites-Derived Exosomes as a Predictor of Survival and Response to Front-Line Chemotherapeutics in Advanced High-Grade Serous Ovarian Cancer
title_full Dynamic Monitoring of CD200 Mediated by Ascites-Derived Exosomes as a Predictor of Survival and Response to Front-Line Chemotherapeutics in Advanced High-Grade Serous Ovarian Cancer
title_fullStr Dynamic Monitoring of CD200 Mediated by Ascites-Derived Exosomes as a Predictor of Survival and Response to Front-Line Chemotherapeutics in Advanced High-Grade Serous Ovarian Cancer
title_full_unstemmed Dynamic Monitoring of CD200 Mediated by Ascites-Derived Exosomes as a Predictor of Survival and Response to Front-Line Chemotherapeutics in Advanced High-Grade Serous Ovarian Cancer
title_short Dynamic Monitoring of CD200 Mediated by Ascites-Derived Exosomes as a Predictor of Survival and Response to Front-Line Chemotherapeutics in Advanced High-Grade Serous Ovarian Cancer
title_sort dynamic monitoring of cd200 mediated by ascites derived exosomes as a predictor of survival and response to front line chemotherapeutics in advanced high grade serous ovarian cancer
topic exosome
ovarian cancer
cd200
prognosis
response
url https://www.imrpress.com/journal/CEOG/50/10/10.31083/j.ceog5010217
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