Overexpression of G protein-coupled receptor 5D in the bone marrow is associated with poor prognosis in patients with multiple myeloma

Eur J Clin Invest. 2012 Sep;42(9):953-60. doi: 10.1111/j.1365-2362.2012.02679.x. Epub 2012 May 16.

Abstract

Background: G protein-coupled receptor 5D (GPRC5D) is a novel surface receptor. As this new subtype of G protein-coupled receptors was discovered, little is known about the role of this gene.

Materials and methods: In this retrospective study, we investigated GPRC5D mRNA expression by real-time polymerase chain reaction (RT-PCR) in bone marrow (BM) of 48 patients with multiple myeloma (MM).

Results: Highly variable levels of GPRC5D (median, 288; quartiles, 17-928) were detected in patients with MM, whereas only low expression was detected in normal tissues (median, 1; quartiles, 1-23). High mRNA expression of GPRC5D correlated positively with high plasma cell count in bone marrow (r = 0·64, P < 0·001), high β(2) -microglobulin (r = 0·42, P = 0·003) and poor-risk cytogenetics: deletion 13q14 (rb-1), P = 0·003; and 14q32 translocation t(4;14)(p16;q32), P = 0·029. GPRC5D mRNA expression showed a significant correlation with overall survival (P = 0·031). The estimated overall survival of patients expressing GPRC5D above or below the median of 288 was 43·9% vs. 70·2% at 48 months. Here, we report, for the first time, the association of GPRC5D expression and cancer.

Conclusions: Overexpression in poor-risk myeloma, low expression in normal tissues and cell surface expression identify GPRC5D as a potential novel cancer antigen. Our data demonstrate that GPRC5D is a prognostic factor in MM correlating with other major risk factors.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Marrow / metabolism*
  • Cytogenetics
  • Female
  • Gene Expression Regulation / physiology*
  • Humans
  • Male
  • Middle Aged
  • Multiple Myeloma / genetics*
  • Prognosis
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Receptors, G-Protein-Coupled / genetics*
  • Retrospective Studies
  • Risk Factors
  • Statistics as Topic
  • Translocation, Genetic

Substances

  • GPRC5D protein, human
  • RNA, Messenger
  • Receptors, G-Protein-Coupled