Autophagic Markers BECLIN 1 and LC3 are Associated with Prognosis of Multiple Myeloma

Acta Haematol. 2015;134(1):17-24. doi: 10.1159/000368848. Epub 2015 Apr 3.

Abstract

Background/aims: Autophagy is crucial for the survival and function of plasma cells including protection from toxic misfolded immunoglobulin and proper energy metabolism. Multiple myeloma (MM) is an indolent but eventually fatal neoplasm of plasma cells. Autophagy may play a critical role in the survival of MM cells and their response to chemotherapeutic agents. In this study, we correlated the expression of autophagy-related proteins with the prognosis of MM.

Methods: In this retrospective cohort study, we examined the expression of the autophagic markers BECLIN 1 and microtubule-associated protein light chain 3 (LC3) in 89 cases of MM biopsied from 2001 to 2004 at the Asan Medical Center. The association of the expression scores of these markers with clinical outcomes was assessed.

Results: Patients with strong immunoreactivity to BECLIN 1 or LC3 had a significantly better overall survival (OS) than patients with negative to moderate immunoreactivity (p = 0.036 and 0.018, respectively). This was also true for disease-specific survival (DSS; p = 0.051 and 0.043, respectively). In addition, LC3 immunostaining remained an independent factor impacting OS (p = 0.028) and DSS (p = 0.020) after multivariate analysis.

Conclusions: The results of this study suggest that higher immunoreactivity for autophagic markers in MM is associated with superior patient survival.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis Regulatory Proteins / biosynthesis*
  • Autophagy*
  • Beclin-1
  • Biomarkers, Tumor / biosynthesis*
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Membrane Proteins / biosynthesis*
  • Microtubule-Associated Proteins / biosynthesis*
  • Middle Aged
  • Multiple Myeloma / metabolism*
  • Multiple Myeloma / mortality*
  • Multiple Myeloma / pathology
  • Multiple Myeloma / therapy
  • Neoplasm Proteins / biosynthesis*
  • Retrospective Studies
  • Survival Rate

Substances

  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • Beclin-1
  • Biomarkers, Tumor
  • MAP1LC3A protein, human
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins