Prediction of Therapeutic Response and Prognosis in Ovarian Cancer Patients With Plasma Circulating Biomarkers

ABSTRACT Background To assess whether changes in TP53 mutations and copy number alterations (CNA) in plasma circulating tumor DNA (ctDNA) can predict treatment response and prognosis in platinum‐resistant recurrent ovarian cancer (PROC) patients. Methods Fifty‐seven PROC patients were recruited. For...

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Main Authors: Haixia Cheng, Guangwen Yuan, Leilei Liang, Tiantian Wang, Jiarun Zhu, Hongying Yang, Zhendiao Zhou, Pei Wang, Qianqian Song, Yuchen Jiao, Mei Liu, Lingying Wu
Format: Article
Language:English
Published: Wiley 2025-08-01
Series:Cancer Innovation
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Online Access:https://doi.org/10.1002/cai2.70014
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author Haixia Cheng
Guangwen Yuan
Leilei Liang
Tiantian Wang
Jiarun Zhu
Hongying Yang
Zhendiao Zhou
Pei Wang
Qianqian Song
Yuchen Jiao
Mei Liu
Lingying Wu
author_facet Haixia Cheng
Guangwen Yuan
Leilei Liang
Tiantian Wang
Jiarun Zhu
Hongying Yang
Zhendiao Zhou
Pei Wang
Qianqian Song
Yuchen Jiao
Mei Liu
Lingying Wu
author_sort Haixia Cheng
collection DOAJ
description ABSTRACT Background To assess whether changes in TP53 mutations and copy number alterations (CNA) in plasma circulating tumor DNA (ctDNA) can predict treatment response and prognosis in platinum‐resistant recurrent ovarian cancer (PROC) patients. Methods Fifty‐seven PROC patients were recruited. Forty‐three patients with matched tumor and plasma samples were analyzed via both a tumor‐informed ctDNA assay (TICA) and a tumor‐uninformed ctDNA assay (TUCA) profiling TP53 mutations and CNA. The TUCA algorithm was optimized based on TICA results. Fourteen patients without matched tumor tissues were used just for TUCA analysis. Results A ctDNA decrease of ≥ 80% from baseline or ctDNA negativity during treatment detected by the TICA (defined as favorable TICA changes) strategy before the third cycle predicted the best overall response, with 81.8% sensitivity and 84.6% specificity. The TUCA strategy was defined as a combination of TP53 mutations and CNA changes. A favorable TUCA change before the third cycle predicted the best overall response, with 90.0% sensitivity and 63.2% specificity. In 12 patients without clinical benefit, the median lead time to detect drug resistance from TUCA to the Response Evaluation Criteria in Solid Tumors was 86.0 days. Patients with favorable ctDNA changes (n = 15) detected by TUCA before the third cycle had a median progression‐free survival of 9.2 months, versus 3.6 months in those without (n = 34) (HR: 2.88; 95% CI 1.56–5.30; log‐rank p = 0.0008). Conclusions Similar to TICA, ctDNA changes detected by TUCA combined with TP53 mutations and CNA could predict treatment response and prognosis in PROC patients without requiring tumor tissues.
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spelling doaj-art-4397fc72133446a6bf1ce3d1020fa93d2025-08-20T03:28:54ZengWileyCancer Innovation2770-91912770-91832025-08-0144n/an/a10.1002/cai2.70014Prediction of Therapeutic Response and Prognosis in Ovarian Cancer Patients With Plasma Circulating BiomarkersHaixia Cheng0Guangwen Yuan1Leilei Liang2Tiantian Wang3Jiarun Zhu4Hongying Yang5Zhendiao Zhou6Pei Wang7Qianqian Song8Yuchen Jiao9Mei Liu10Lingying Wu11Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Gynecologic Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Gynecologic Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Gynecologic Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaLaboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaPeking University Cancer Hospital Yunnan Hospital/Yunnan Provincial Cancer Hospital/The Third Affiliated Hospital of Kunming Medical University Kunming Yunnan ChinaLaboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaLaboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaLaboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaLaboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaLaboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Gynecologic Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaABSTRACT Background To assess whether changes in TP53 mutations and copy number alterations (CNA) in plasma circulating tumor DNA (ctDNA) can predict treatment response and prognosis in platinum‐resistant recurrent ovarian cancer (PROC) patients. Methods Fifty‐seven PROC patients were recruited. Forty‐three patients with matched tumor and plasma samples were analyzed via both a tumor‐informed ctDNA assay (TICA) and a tumor‐uninformed ctDNA assay (TUCA) profiling TP53 mutations and CNA. The TUCA algorithm was optimized based on TICA results. Fourteen patients without matched tumor tissues were used just for TUCA analysis. Results A ctDNA decrease of ≥ 80% from baseline or ctDNA negativity during treatment detected by the TICA (defined as favorable TICA changes) strategy before the third cycle predicted the best overall response, with 81.8% sensitivity and 84.6% specificity. The TUCA strategy was defined as a combination of TP53 mutations and CNA changes. A favorable TUCA change before the third cycle predicted the best overall response, with 90.0% sensitivity and 63.2% specificity. In 12 patients without clinical benefit, the median lead time to detect drug resistance from TUCA to the Response Evaluation Criteria in Solid Tumors was 86.0 days. Patients with favorable ctDNA changes (n = 15) detected by TUCA before the third cycle had a median progression‐free survival of 9.2 months, versus 3.6 months in those without (n = 34) (HR: 2.88; 95% CI 1.56–5.30; log‐rank p = 0.0008). Conclusions Similar to TICA, ctDNA changes detected by TUCA combined with TP53 mutations and CNA could predict treatment response and prognosis in PROC patients without requiring tumor tissues.https://doi.org/10.1002/cai2.70014circulating tumor DNAcopy number alterationsovarian cancerTP53 mutations
spellingShingle Haixia Cheng
Guangwen Yuan
Leilei Liang
Tiantian Wang
Jiarun Zhu
Hongying Yang
Zhendiao Zhou
Pei Wang
Qianqian Song
Yuchen Jiao
Mei Liu
Lingying Wu
Prediction of Therapeutic Response and Prognosis in Ovarian Cancer Patients With Plasma Circulating Biomarkers
Cancer Innovation
circulating tumor DNA
copy number alterations
ovarian cancer
TP53 mutations
title Prediction of Therapeutic Response and Prognosis in Ovarian Cancer Patients With Plasma Circulating Biomarkers
title_full Prediction of Therapeutic Response and Prognosis in Ovarian Cancer Patients With Plasma Circulating Biomarkers
title_fullStr Prediction of Therapeutic Response and Prognosis in Ovarian Cancer Patients With Plasma Circulating Biomarkers
title_full_unstemmed Prediction of Therapeutic Response and Prognosis in Ovarian Cancer Patients With Plasma Circulating Biomarkers
title_short Prediction of Therapeutic Response and Prognosis in Ovarian Cancer Patients With Plasma Circulating Biomarkers
title_sort prediction of therapeutic response and prognosis in ovarian cancer patients with plasma circulating biomarkers
topic circulating tumor DNA
copy number alterations
ovarian cancer
TP53 mutations
url https://doi.org/10.1002/cai2.70014
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