Clinical epigenetics · 2021
5-Hydroxymethylcytosine profiles of cfDNA are highly predictive of R-CHOP treatment response in diffuse large B cell lymphoma patients.
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Chen Hang-Yu, Zhang Wei-Long, Zhang Lei, Yang Ping, Li Fang, Yang Ze-Ruo, Wang Jing, Pang Meng, Hong Yun, Yan Changjian, Li Wei, Liu Jia, Xu Nuo, Chen Long, Xiao Xiu-Bing, Qin Yan, He Xiao-Hui, Liu Hui, Zhu Hai-Chuan, He Chuan, Lin Jian, Jing Hong-Mei
Аннотация
BACKGROUND: Although R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) remains the standard chemotherapy regimen for diffuse large B cell lymphoma (DLBCL) patients, not all patients are responsive to the scheme, and there is no effective method to predict treatment response.
METHODS: We utilized 5hmC-Seal to generate genome-wide 5hmC profiles in plasma cell-free DNA (cfDNA) from 86 DLBCL patients before they received R-CHOP chemotherapy. To investigate the correlation between 5hmC modifications and curative effectiveness, we separated patients into training (n = 56) and validation (n = 30) cohorts and developed a 5hmC-based logistic regression model from the training cohort to predict the treatment response in the validation cohort.
RESULTS: In this study, we identified thirteen 5hmC markers associated with treatment response. The prediction performance of the logistic regression model, achieving 0.82 sensitivity and 0.75 specificity (AUC = 0.78), was superior to existing clinical indicators, such as LDH and stage.
CONCLUSIONS: Our findings suggest that the 5hmC modifications in cfDNA at the time before R-CHOP treatment are associated with treatment response and that 5hmC-Seal may potentially serve as a clinical-applicable, minimally invasive approach to predict R-CHOP treatment response for DLBCL patients.
METHODS: We utilized 5hmC-Seal to generate genome-wide 5hmC profiles in plasma cell-free DNA (cfDNA) from 86 DLBCL patients before they received R-CHOP chemotherapy. To investigate the correlation between 5hmC modifications and curative effectiveness, we separated patients into training (n = 56) and validation (n = 30) cohorts and developed a 5hmC-based logistic regression model from the training cohort to predict the treatment response in the validation cohort.
RESULTS: In this study, we identified thirteen 5hmC markers associated with treatment response. The prediction performance of the logistic regression model, achieving 0.82 sensitivity and 0.75 specificity (AUC = 0.78), was superior to existing clinical indicators, such as LDH and stage.
CONCLUSIONS: Our findings suggest that the 5hmC modifications in cfDNA at the time before R-CHOP treatment are associated with treatment response and that 5hmC-Seal may potentially serve as a clinical-applicable, minimally invasive approach to predict R-CHOP treatment response for DLBCL patients.
Предметные рубрики MeSH
5-MethylcytosineAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, PharmacologicalCell-Free Nucleic AcidsCohort StudiesCyclophosphamideDNA DemethylationDoxorubicinFemaleHumansLogistic ModelsLymphoma, Large B-Cell, DiffuseMaleMiddle AgedPredictive Value of TestsPrednisoneRituximabSensitivity and SpecificityVincristine