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Clin Epigenetics ; 13(1): 33, 2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33573703

RESUMO

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.


Assuntos
5-Metilcitosina/análogos & derivados , Protocolos de Quimioterapia Combinada Antineoplásica/metabolismo , Ácidos Nucleicos Livres/metabolismo , Linfoma Difuso de Grandes Células B/tratamento farmacológico , 5-Metilcitosina/sangue , 5-Metilcitosina/metabolismo , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Farmacológicos/metabolismo , Estudos de Coortes , Ciclofosfamida/metabolismo , Ciclofosfamida/uso terapêutico , Desmetilação do DNA/efeitos dos fármacos , Doxorrubicina/metabolismo , Doxorrubicina/uso terapêutico , Feminino , Humanos , Modelos Logísticos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/metabolismo , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prednisona/metabolismo , Prednisona/uso terapêutico , Rituximab/metabolismo , Rituximab/uso terapêutico , Sensibilidade e Especificidade , Vincristina/metabolismo , Vincristina/uso terapêutico
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