C-MYC aberrations as prognostic factors in diffuse large B-cell lymphoma: a meta-analysis of epidemiological studies

PLoS One. 2014 Apr 16;9(4):e95020. doi: 10.1371/journal.pone.0095020. eCollection 2014.

Abstract

Objectives: Various 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.

Methods: The 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.

Results: Twenty-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.

Conclusion: The 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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Antibodies, Monoclonal, Murine-Derived / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • DNA Copy Number Variations
  • Disease-Free Survival
  • Epidemiologic Studies
  • Gene Amplification*
  • Gene Rearrangement*
  • Genes, myc / genetics*
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / diagnosis
  • Lymphoma, Large B-Cell, Diffuse / drug therapy
  • Lymphoma, Large B-Cell, Diffuse / genetics*
  • Multivariate Analysis
  • Outcome Assessment, Health Care / statistics & numerical data
  • Prognosis
  • Proportional Hazards Models
  • Rituximab

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Rituximab

Grants and funding

This study was sponsored by the Program of the National Natural Science Foundation of China (Grant No. 81270599). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.