Prognostic significances of overexpression MYC and/or BCL2 in R-CHOP-treated diffuse large B-cell lymphoma: A Systematic review and meta-analysis

Lu Li,Qian Gao,Xue Gao,Mingxing Yu,Kaili Ma,Ximei Que,Yanfeng Xi,Yanyan Li,Tong Wang

doi:10.1038/s41598-018-24631-5

Lu Li, Qian Gao + Show 7 more

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https://doi.org/10.1038/s41598-018-24631-5

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Abstract

Numerous studies have investigated the prognostic values of MYC and/or BCL2 protein overexpression in diffuse large B-cell lymphoma (DLBCL). However, the results still demonstrate discrepancies among different studies. We aimed to do a systematic review and meta-analysis on the relationships between overexpression MYC and/or BCL2 and DLBCLs treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). This study followed the guidelines of PRISMA and Cochrane handbook. The hazard ratios (HRs) for overall survival (OS) were pooled to estimate the main effect size. Twenty studies recruited a total of 5576 patients were available for this meta-analysis. The results showed that MYC (HR = 1.96, 95%CI (confidence interval) = 1.69–2.27)without heterogeneity(I2 = 17.2%, P = 0.280), BCL2 (HR = 1.65, 95%CI = 1.43–1.89, I2 = 20.7%, P = 0.234) protein overexpression, and co-overexpression (HR = 2.58, 95%CI = 2.19–3.04, I2 = 17.2%, P = 0.275) had a poor prognosis in R-CHOP treated DLBCL patients, respectively. The current analysis indicated that MYC and/or BCL2 protein overexpression, and particularly co-overexpression was related to short overall survival in R-CHOP treated DLBCL patients, showing that application of the two new biomarkers can help to better stratify DLBCL patients and guide targeted treatment.

Highlights

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of aggressive non-Hodgkin lymphoma (NHL) and a highly heterogeneous malignancy of B cells both biologically and clinically[1]
Earlier studies reported the poor prognosis of MYC and BCL2 and/or BCL6 rearrangements in diffuse large B-cell lymphoma (DLBCL), known as double-hit lymphoma (DHL), or triple hit lymphoma (THL) by using fluorescent in situ hybridization (FISH) cytogenetic techniques
Most of the studies used the method of IHC to measure the gene expression, while only one study used the method of Array Plate quantitative nuclease protection assay technology

Summary

Introduction

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of aggressive non-Hodgkin lymphoma (NHL) and a highly heterogeneous malignancy of B cells both biologically and clinically[1]. In 2016, the World Health Organization (WHO) revision of the lymphoma classification defined this as a new category of high-grade B-cell lymphoma (HGBL)[7]. This new type of HGBL occurred in less than 10% DLBCL patients. The co-overexpression of MYC and BCL2 and/or BCL6 proteins, so-called dual expressors (DE-DLBCL) or triple expressors(TE-DLBCL) detected by Immunohistochemistry(IHC) is much more common, occurring in 20–30% DLBCL patients. This higher percentage scope may make detailed subdivisions of patients. The systematic review and meta-analysis aims to illuminate the prognostic values of MYC and/or BCL2 overexpression in R-CHOP-treated DLBCL patients

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