Methylome Variation Predicts Exemestane Resistance in Advanced ER+ Breast Cancer
| Autor: | Yuan Fu, Hope S. Rugo, Guo-bing Xu, Lingbo Chen, Huiping Li, Weiyao Kong, Guohong Song, Bin Shao, Hanfang Jiang, Hao Gong, Fengling Wan, Jianwei Che, Jian Tie, Xiaoran Liu, Ruyan Zhang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Adult
Cancer Research medicine.drug_class medicine.medical_treatment methylomes Breast Neoplasms lcsh:RC254-282 03 medical and health sciences chemistry.chemical_compound Epigenome 0302 clinical medicine Exemestane Er breast cancer medicine Humans 030304 developmental biology Aged advanced breast cancer circulating tumor DNA 0303 health sciences exemestane resistance business.industry Aromatase Inhibitors Estrogen Receptor alpha Middle Aged lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Progression-Free Survival Androstadienes Oncology chemistry Estrogen Circulating tumor DNA Drug Resistance Neoplasm 030220 oncology & carcinogenesis DNA methylation Cancer research Original Article Female Hormone therapy business |
| Zdroj: | Technology in Cancer Research & Treatment Technology in Cancer Research & Treatment, Vol 19 (2020) |
| ISSN: | 1533-0338 1533-0346 |
| Popis: | Background: More than 30% of estrogen receptor-positive breast cancers are resistant to primary hormone therapy, and about 40% that initially respond to hormone therapy eventually acquire resistance. Although the mechanisms of hormone therapy resistance remain unclear, aberrant DNA methylation has been implicated in oncogenesis and drug resistance. Purpose: We investigated the relationship between methylome variations in circulating tumor DNA and exemestane resistance, to track hormone therapy efficacy. Methods: We prospectively recruited 16 patients who were receiving first-line therapy in our center. All patients received exemestane-based hormone therapy after enrollment. We collected blood samples at baseline, first follow-up (after 2 therapeutic cycles) and at detection of disease progression. Disease that progressed within 6 months under exemestane treatment was considered exemestane resistance but was considered relatively exemestane-sensitive otherwise. We obtained circulating tumor DNA-derived methylomes using the whole-genome bisulfide sequencing method. Methylation calling was done by BISMARK software; differentially methylated regions for exemestane resistance were calculated afterward. Results: Median follow-up for the 16 patients was 19.0 months. We found 7 exemestane resistance-related differentially methylated regions, located in different chromosomes, with both significantly different methylation density and methylation ratio. Baseline methylation density and methylation ratio of chromosome 6 [32400000-32599999] were both high in exemestane resistance. High baseline methylation ratios of chromosome 3 [67800000-67999999] ( P = .013), chromosome 3 [140200000-140399999] ( P = .037), and chromosome 12 [101200000-101399999] ( P = .026) could also predict exemestane resistance. During exemestane treatment, synchronized changes in methylation density and methylation ratio in chromosome 6 [32400000-32599999] could accurately stratify patients in terms of progression-free survival ( P = .000033). Cutoff values of methylation density and methylation ratio for chromosome 6 [149600000-149799999] were 0.066 and 0.076, respectively. Conclusion: Methylation change in chromosome 6 [149600000-149799999] is an ideal predictor of exemestane resistance with great clinical potential. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|