Abstract
ObjectivesVarious studies have investigated the prognostic value of C-MYC aberrations in diffuse large B-cell lymphoma (DLBCL). However, the role of C-MYC as an independent prognostic factor in clinical practice remains controversial. A systematic review and meta-analysis were performed to clarify the clinical significance of C-MYC aberrations in DLBCL patients.MethodsThe pooled hazard ratios (HRs) for overall survival (OS) and event-free survival (EFS) were calculated as the main effect size estimates. The procedure was conducted according to the Cochrane handbook and PRISMA guidelines, including the use of a heterogeneity test, publication bias assessment, and meta-regression, as well as subgroup analyses.ResultsTwenty-four eligible studies enrolling 4662 patients were included in this meta-analysis. According to the nature of C-MYC aberrations (gene, protein, and mRNA), studies were divided into several subgroups. For DLBCL patients with C-MYC gene abnormalities, the combined HR was 2.22 (95% confidence interval, 1.89 to 2.61) for OS and 2.29 (95% confidence interval, 1.81 to 2.90) for EFS, compared to patients without C-MYC gene abnormalities. For DLBCL patients with overexpression of C-MYC protein and C-MYC mRNA, pooled HRs for OS were 2.13 and 1.62, respectively. C-MYC aberrations appeared to play an independent role among other well-known prognostic factors in DLBCL. Addition of rituximab could not overcome the inferior prognosis conferred by C-MYC.ConclusionThe present systematic review and meta-analysis confirm the prognostic value of C-MYC aberrations. Screening of C-MYC should have definite prognostic meaning for DLBCL stratification, thus guaranteeing a more tailored therapy.
Highlights
Non-Hodgkin lymphoma (NHL) is the fifth most frequent cancer worldwide, in which diffuse large B-cell lymphoma (DLBCL) ranks the most common histologic subtype
According to the PRISMA guidelines [31], studies included in this meta-analysis should meet the following criteria: (i) C-MYC aberrations in adult patients with primary DLBCL had been examined by fluorescent in situ hybridization (FISH), immunohistochemistry (IHC) or other techniques; (ii) detailed survival information was available; and (iii) the median follow-up time exceeded one year
Gupta et al and Horn et al evaluated the association of survival endpoints with both C-MYC gene translocation and C-MYC protein overexpression in DLBCL [11,26]
Summary
Non-Hodgkin lymphoma (NHL) is the fifth most frequent cancer worldwide, in which diffuse large B-cell lymphoma (DLBCL) ranks the most common histologic subtype. DLBCL comprises a heterogeneous group with varied clinical and molecular features and different prognoses, despite uniform treatment. Recognition of the biological heterogeneity of DLBCL is of clinical importance [1]. The International Prognostic Index (IPI) is currently the most well-established index for risk stratification of DLBCL patients [2]. This prognostic index has limitations in reflecting the biologic or genetic features of DLBCL. Even within the same IPI risk group, substantial variability in clinical outcome has been observed. The prognosis in high-risk DLBCL patients remains dismal. Identification and validation of novel prognostic biomarkers may contribute to better stratification of DLBCL and guide optimal treatment
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