Prediction and prognostic significance of BCAR3 expression in patients with multiple myeloma

J Transl Med. 2018 Dec 18;16(1):363. doi: 10.1186/s12967-018-1728-8.

Abstract

Background: Multiple myeloma (MM) is the plasma cell tumor, which is characterized by clonal proliferation of tumor cells, with high risk of progression to renal impairment, bone damage and amyloidosis. Although the survival rate of patients with MM has improved in the past decade, most people inevitably relapse. The treatment and prognosis of MM are still urgent problems. Breast Cancer Antiestrogen Resistance 3 (BCAR3) is a protein-coding gene that is associated with many tumors. However, there have been few studies on the relationship of BCAR3 and MM.

Methods: We analyzed 1878 MM patients (1930 samples) from 7 independent datasets. First, we compared the BCAR3 expression level of MM patients in different stages and MM patients with different amplification of 1q21. Second, we analyzed BCAR3 expression levels in MM patients with different molecular subtypes. Finally, we explored the event-free survival rate (EFS) and overall survival rate (OS) of MM patients with high or low BCAR3 expression, including patients before and after relapse, and their therapeutic responses to bortezomib and dexamethasone.

Results: The expression of BCAR3 showed a decreasing trend in stages I, II and III (P = 0.00068). With the increase of 1q21 amplification level, the expression of BCAR3 decreased (P = 0.022). Patients with high BCAR3 expression had higher EFS and OS (EFS: P < 0.0001, OS: P < 0.0001). The expression of BCAR3 gene before relapse was higher than that after relapse (P = 0.0045). BCAR3 is an independent factor affecting prognosis (EFS: P = 5.17E-03; OS: P = 3.33E-04).

Conclusion: We found that high expression level of BCAR3 predicted better prognosis of MM patients. Low expression of BCAR3 at diagnosis can predict early relapse. BCAR3 is an independent prognostic factor for MM. BCAR3 can be used as a potential biomarker.

Keywords: BCAR3; Gene expression profile; Multiple myeloma; Prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Bortezomib / pharmacology
  • Bortezomib / therapeutic use
  • Dexamethasone / pharmacology
  • Dexamethasone / therapeutic use
  • Gene Amplification / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Guanine Nucleotide Exchange Factors
  • Humans
  • Immunity / drug effects
  • Multiple Myeloma / drug therapy
  • Multiple Myeloma / genetics
  • Multiple Myeloma / immunology
  • Multiple Myeloma / metabolism*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Prognosis
  • Survival Analysis

Substances

  • Adaptor Proteins, Signal Transducing
  • BCAR3 protein, human
  • Guanine Nucleotide Exchange Factors
  • Bortezomib
  • Dexamethasone