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Homologous recombination deficiency status predicts response to platinum-based chemotherapy in Chinese patients with high-grade serous ovarian carcinoma

BACKGROUND: Homologous Recombination Deficiency (HRD) is a predictive biomarker for ovarian cancer treated with PARP inhibitors or for breast cancer treated with first-line platinum-based chemotherapy. However, limited research is documented on platinum-based treatment prediction with HRD as a bioma...

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Autores principales: Feng, Zheng, Shao, Di, Cai, Yuhang, Bi, Rui, Ju, Xingzhu, Chen, Dongju, Song, Chengcheng, Chen, Xiaojun, Li, Jin, An, Na, Li, Yunjin, Zhou, Qing, Xiu, Zhihui, Zhu, Shida, Wu, Xiaohua, Wen, Hao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10015784/
https://www.ncbi.nlm.nih.gov/pubmed/36922847
http://dx.doi.org/10.1186/s13048-023-01129-x
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author Feng, Zheng
Shao, Di
Cai, Yuhang
Bi, Rui
Ju, Xingzhu
Chen, Dongju
Song, Chengcheng
Chen, Xiaojun
Li, Jin
An, Na
Li, Yunjin
Zhou, Qing
Xiu, Zhihui
Zhu, Shida
Wu, Xiaohua
Wen, Hao
author_facet Feng, Zheng
Shao, Di
Cai, Yuhang
Bi, Rui
Ju, Xingzhu
Chen, Dongju
Song, Chengcheng
Chen, Xiaojun
Li, Jin
An, Na
Li, Yunjin
Zhou, Qing
Xiu, Zhihui
Zhu, Shida
Wu, Xiaohua
Wen, Hao
author_sort Feng, Zheng
collection PubMed
description BACKGROUND: Homologous Recombination Deficiency (HRD) is a predictive biomarker for ovarian cancer treated with PARP inhibitors or for breast cancer treated with first-line platinum-based chemotherapy. However, limited research is documented on platinum-based treatment prediction with HRD as a biomarker in ovarian cancer patients, especially in the Chinese population. METHODS: We investigated the association between HRD status and the response of platinum-based chemotherapy in 240 Chinese HGSOC patients. RESULTS: The Pt-sensitive patients showed higher HRD scores than Pt-resistant ones, but this was not significant(median: 42.6 vs. 31.6, p = 0.086). (Pt)-sensitive rate was higher in HRD + BRCAm tumors and in HRD + BRCAwt tumors (HRD + BRCAm: 97%, p = 0.004 and HRD + BRCAwt: 90%, p = 0.04) compared with 74% in the HRD-BRCAwt tumors. We also found Pt-sensitive patients tend to be enriched in patients with BRCA mutations or non-BRCA HRR pathway gene mutations (BRCA: 93.6% vs 75.4%, p < 0.001; non-BRCA HRR: 88.6% vs 75.4%, p = 0.062). Patients with HRD status positive had significantly improved PFS compared with those with HRD status negative (median PFS: 30.5 months vs. 16.8 months, Log-rank p = 0.001). Even for BRCAwt patients, positive HRD was also associated with better PFS than the HRD-negative group (median: 27.5 months vs 16.8 months, Log-rank p = 0.010). Further, we found patients with pathogenic mutations located in the DNA-binding domain (DBD) of BRCA1 had improved FPS, compared to those with mutations in other domains. (p = 0.03). CONCLUSIONS: The HRD status can be identified as an independent significance in Chinese HGSOC patients treated with first-line platinum-based chemotherapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13048-023-01129-x.
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spelling pubmed-100157842023-03-16 Homologous recombination deficiency status predicts response to platinum-based chemotherapy in Chinese patients with high-grade serous ovarian carcinoma Feng, Zheng Shao, Di Cai, Yuhang Bi, Rui Ju, Xingzhu Chen, Dongju Song, Chengcheng Chen, Xiaojun Li, Jin An, Na Li, Yunjin Zhou, Qing Xiu, Zhihui Zhu, Shida Wu, Xiaohua Wen, Hao J Ovarian Res Research BACKGROUND: Homologous Recombination Deficiency (HRD) is a predictive biomarker for ovarian cancer treated with PARP inhibitors or for breast cancer treated with first-line platinum-based chemotherapy. However, limited research is documented on platinum-based treatment prediction with HRD as a biomarker in ovarian cancer patients, especially in the Chinese population. METHODS: We investigated the association between HRD status and the response of platinum-based chemotherapy in 240 Chinese HGSOC patients. RESULTS: The Pt-sensitive patients showed higher HRD scores than Pt-resistant ones, but this was not significant(median: 42.6 vs. 31.6, p = 0.086). (Pt)-sensitive rate was higher in HRD + BRCAm tumors and in HRD + BRCAwt tumors (HRD + BRCAm: 97%, p = 0.004 and HRD + BRCAwt: 90%, p = 0.04) compared with 74% in the HRD-BRCAwt tumors. We also found Pt-sensitive patients tend to be enriched in patients with BRCA mutations or non-BRCA HRR pathway gene mutations (BRCA: 93.6% vs 75.4%, p < 0.001; non-BRCA HRR: 88.6% vs 75.4%, p = 0.062). Patients with HRD status positive had significantly improved PFS compared with those with HRD status negative (median PFS: 30.5 months vs. 16.8 months, Log-rank p = 0.001). Even for BRCAwt patients, positive HRD was also associated with better PFS than the HRD-negative group (median: 27.5 months vs 16.8 months, Log-rank p = 0.010). Further, we found patients with pathogenic mutations located in the DNA-binding domain (DBD) of BRCA1 had improved FPS, compared to those with mutations in other domains. (p = 0.03). CONCLUSIONS: The HRD status can be identified as an independent significance in Chinese HGSOC patients treated with first-line platinum-based chemotherapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13048-023-01129-x. BioMed Central 2023-03-15 /pmc/articles/PMC10015784/ /pubmed/36922847 http://dx.doi.org/10.1186/s13048-023-01129-x Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Feng, Zheng
Shao, Di
Cai, Yuhang
Bi, Rui
Ju, Xingzhu
Chen, Dongju
Song, Chengcheng
Chen, Xiaojun
Li, Jin
An, Na
Li, Yunjin
Zhou, Qing
Xiu, Zhihui
Zhu, Shida
Wu, Xiaohua
Wen, Hao
Homologous recombination deficiency status predicts response to platinum-based chemotherapy in Chinese patients with high-grade serous ovarian carcinoma
title Homologous recombination deficiency status predicts response to platinum-based chemotherapy in Chinese patients with high-grade serous ovarian carcinoma
title_full Homologous recombination deficiency status predicts response to platinum-based chemotherapy in Chinese patients with high-grade serous ovarian carcinoma
title_fullStr Homologous recombination deficiency status predicts response to platinum-based chemotherapy in Chinese patients with high-grade serous ovarian carcinoma
title_full_unstemmed Homologous recombination deficiency status predicts response to platinum-based chemotherapy in Chinese patients with high-grade serous ovarian carcinoma
title_short Homologous recombination deficiency status predicts response to platinum-based chemotherapy in Chinese patients with high-grade serous ovarian carcinoma
title_sort homologous recombination deficiency status predicts response to platinum-based chemotherapy in chinese patients with high-grade serous ovarian carcinoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10015784/
https://www.ncbi.nlm.nih.gov/pubmed/36922847
http://dx.doi.org/10.1186/s13048-023-01129-x
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