5-Hydroxymethylcytosine profiles of cfDNA are highly predictive of R-CHOP treatment response in diffuse large B cell lymphoma patients

Hangyu Chen ,Long Chen,Yun Hong,Jian Lin,Xiaohong He ,Zeruo Yang ,Lei Zhang,Fang Li,Wei Li,Haichuan Zhu ,Changjian Yan,Nuo Xu,Jing Wang,Weilong Zhang ,Chuan He,Pei Meng ,Ping Yang,Hui Liu,Jia Liu,Xiu-Bing Xiao,Yan Qin,Hongmei Jing

doi:10.1186/s13148-020-00973-8

Abstract

BackgroundAlthough 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.MethodsWe 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.ResultsIn 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.ConclusionsOur 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.

Highlights

Diffuse large B cell lymphoma (DLBCL) is the primary type of invasive lymphoid tissue tumor, accounting for about 30% of non-Hodgkin’s lymphoma [1]
Treatment efficacy was evaluated after four cycles of treatment according to Lugano 2014 criteria [28], and patients were divided into Progressive disease (PD), Stable disease (SD), Partial response (PR), and Complete response (CR) based on the treatment outcome
The results of the international prognostic index (IPI) score showed that 52.3% of patients (IPI score > 2) belonged to the high–intermediate-risk/high-risk group

Summary

Introduction

Diffuse large B cell lymphoma (DLBCL) is the primary type of invasive lymphoid tissue tumor, accounting for about 30% of non-Hodgkin’s lymphoma [1]. Recent studies have demonstrated that the detection of the apoptosis inhibitor, survivin [12], activationinduced cytidine deaminase (AID) [13], plasma miRNA [14], exosome miRNA [15], and genes polymorphism [16, 17], as well as the presence of CD3 and FoxP3 in the immune microenvironment [18], were all potential indicators of treatment efficacy in DLBCL patients. 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 respon‐ sive to the scheme, and there is no effective method to predict treatment response

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