Association between the nucleosome footprint of plasma DNA and neoadjuvant chemotherapy response for breast cancer

Abstract Gene expression signatures have been used to predict the outcome of chemotherapy for breast cancer. The nucleosome footprint of cell-free DNA (cfDNA) carries gene expression information of the original tissues and thus may be used to predict the response to chemotherapy. Here we carried out...

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Autores principales:	Xu Yang, Geng-Xi Cai, Bo-Wei Han, Zhi-Wei Guo, Ying-Song Wu, Xiaoming Lyu, Li-Min Huang, Yuan-Bin Zhang, Xin Li, Guo-Lin Ye, Xue-Xi Yang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/8b031bb6976c4e6e965caea8634927ac
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spelling	oai:doaj.org-article:8b031bb6976c4e6e965caea8634927ac2021-12-02T11:44:54ZAssociation between the nucleosome footprint of plasma DNA and neoadjuvant chemotherapy response for breast cancer10.1038/s41523-021-00237-52374-4677https://doaj.org/article/8b031bb6976c4e6e965caea8634927ac2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41523-021-00237-5https://doaj.org/toc/2374-4677Abstract Gene expression signatures have been used to predict the outcome of chemotherapy for breast cancer. The nucleosome footprint of cell-free DNA (cfDNA) carries gene expression information of the original tissues and thus may be used to predict the response to chemotherapy. Here we carried out the nucleosome positioning on cfDNA from 85 breast cancer patients and 85 healthy individuals and two cancer cell lines T-47D and MDA-MB-231 using low-coverage whole-genome sequencing (LCWGS) method. The patients showed distinct nucleosome footprints at Transcription Start Sites (TSSs) compared with normal donors. In order to identify the footprints of cfDNA corresponding with the responses to neoadjuvant chemotherapy in patients, we mapped on nucleosome positions on cfDNA of patients with different responses: responders (pretreatment, n = 28; post-1 cycle, post-3/4 cycles, and post-8 cycles of treatment, n = 12) and nonresponders (pretreatment, n = 10; post-1 cycle, post-3/4 cycles, and post-8 cycles of treatment, n = 10). The coverage depth near TSSs in plasma cfDNA differed significantly between responders and nonresponders at pretreatment, and also after neoadjuvant chemotherapy treatment cycles. We identified 232 TSSs with differential footprints at pretreatment and 321 after treatment and found enrichment in Gene Ontology terms such as cell growth inhibition, tumor suppressor, necrotic cell death, acute inflammatory response, T cell receptor signaling pathway, and positive regulation of vascular endothelial growth factor production. These results suggest that cfDNA nucleosome footprints may be used to predict the efficacy of neoadjuvant chemotherapy for breast cancer patients and thus may provide help in decision making for individual patients.Xu YangGeng-Xi CaiBo-Wei HanZhi-Wei GuoYing-Song WuXiaoming LyuLi-Min HuangYuan-Bin ZhangXin LiGuo-Lin YeXue-Xi YangNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Breast Cancer, Vol 7, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Xu Yang Geng-Xi Cai Bo-Wei Han Zhi-Wei Guo Ying-Song Wu Xiaoming Lyu Li-Min Huang Yuan-Bin Zhang Xin Li Guo-Lin Ye Xue-Xi Yang Association between the nucleosome footprint of plasma DNA and neoadjuvant chemotherapy response for breast cancer
description	Abstract Gene expression signatures have been used to predict the outcome of chemotherapy for breast cancer. The nucleosome footprint of cell-free DNA (cfDNA) carries gene expression information of the original tissues and thus may be used to predict the response to chemotherapy. Here we carried out the nucleosome positioning on cfDNA from 85 breast cancer patients and 85 healthy individuals and two cancer cell lines T-47D and MDA-MB-231 using low-coverage whole-genome sequencing (LCWGS) method. The patients showed distinct nucleosome footprints at Transcription Start Sites (TSSs) compared with normal donors. In order to identify the footprints of cfDNA corresponding with the responses to neoadjuvant chemotherapy in patients, we mapped on nucleosome positions on cfDNA of patients with different responses: responders (pretreatment, n = 28; post-1 cycle, post-3/4 cycles, and post-8 cycles of treatment, n = 12) and nonresponders (pretreatment, n = 10; post-1 cycle, post-3/4 cycles, and post-8 cycles of treatment, n = 10). The coverage depth near TSSs in plasma cfDNA differed significantly between responders and nonresponders at pretreatment, and also after neoadjuvant chemotherapy treatment cycles. We identified 232 TSSs with differential footprints at pretreatment and 321 after treatment and found enrichment in Gene Ontology terms such as cell growth inhibition, tumor suppressor, necrotic cell death, acute inflammatory response, T cell receptor signaling pathway, and positive regulation of vascular endothelial growth factor production. These results suggest that cfDNA nucleosome footprints may be used to predict the efficacy of neoadjuvant chemotherapy for breast cancer patients and thus may provide help in decision making for individual patients.
format	article
author	Xu Yang Geng-Xi Cai Bo-Wei Han Zhi-Wei Guo Ying-Song Wu Xiaoming Lyu Li-Min Huang Yuan-Bin Zhang Xin Li Guo-Lin Ye Xue-Xi Yang
author_facet	Xu Yang Geng-Xi Cai Bo-Wei Han Zhi-Wei Guo Ying-Song Wu Xiaoming Lyu Li-Min Huang Yuan-Bin Zhang Xin Li Guo-Lin Ye Xue-Xi Yang
author_sort	Xu Yang
title	Association between the nucleosome footprint of plasma DNA and neoadjuvant chemotherapy response for breast cancer
title_short	Association between the nucleosome footprint of plasma DNA and neoadjuvant chemotherapy response for breast cancer
title_full	Association between the nucleosome footprint of plasma DNA and neoadjuvant chemotherapy response for breast cancer
title_fullStr	Association between the nucleosome footprint of plasma DNA and neoadjuvant chemotherapy response for breast cancer
title_full_unstemmed	Association between the nucleosome footprint of plasma DNA and neoadjuvant chemotherapy response for breast cancer
title_sort	association between the nucleosome footprint of plasma dna and neoadjuvant chemotherapy response for breast cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8b031bb6976c4e6e965caea8634927ac
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Association between the nucleosome footprint of plasma DNA and neoadjuvant chemotherapy response for breast cancer

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