Association between the nucleosome footprint of plasma DNA and neoadjuvant chemotherapy response for breast cancer
| Autor: | Guo-Lin Ye, Li-Min Huang, Yuanbin Zhang, Ying-Song Wu, Geng-Xi Cai, Zhi-Wei Guo, Xue-Xi Yang, Bo-Wei Han, Xin Li, Xiaoming Lyu, Xu Yang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty medicine.medical_treatment Article law.invention Tumour biomarkers 03 medical and health sciences chemistry.chemical_compound Breast cancer 0302 clinical medicine law Internal medicine Gene expression medicine Nucleosome Pharmacology (medical) Radiology Nuclear Medicine and imaging RC254-282 Chemotherapy Cell growth business.industry Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease 030104 developmental biology chemistry 030220 oncology & carcinogenesis Suppressor Vascular endothelial growth factor production business DNA |
| Zdroj: | NPJ Breast Cancer npj Breast Cancer, Vol 7, Iss 1, Pp 1-12 (2021) |
| ISSN: | 2374-4677 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|