Expression of L-type amino acid transporter 1 (LAT1) as a prognostic and therapeutic indicator in multiple myeloma

Cancer Sci. 2014 Nov;105(11):1496-502. doi: 10.1111/cas.12529. Epub 2014 Oct 9.

Abstract

L-type amino-acid transporter 1 (LAT1) plays a key role in cell growth and survival. To determine the prognostic significance of LAT1 in multiple myeloma (MM), we investigated the expression of LAT1 and its functional subunit, 4Fc heavy chain (CD98), on myeloma cells by immunohistochemistry in 100 newly diagnosed MM patients. High expression (moderate or strong staining intensity) of LAT1 and CD98 was detected in 56% and 45% of patients, respectively. The LAT1 expression score was positively correlated with Ki-67 index (r = 0.631, P < 0.001), and there was a statistically significant difference in Durie-Salmon stage between patients with high and low LAT1 expression (P = 0.03). In 43 patients treated with melphalan and prednisolone, the overall response rate was significantly higher in the high LAT1 expression group (60.0%) than in the low LAT1 expression group (17.6%) (P = 0.03). Multivariate analysis confirmed that high expression of LAT1 was a significant prognostic factor for predicting poor overall survival independently from the International Staging System (both P = 0.01). Here, we show that the overexpression of LAT1 is significantly associated with high proliferation and poor prognosis in newly diagnosed MM patients. Thus, LAT1 may be a promising pathological marker for identifying high-risk MM.

Keywords: CD98; L-type amino-acid transporter 1; melphalan; multiple myeloma; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use
  • Chromosome Aberrations
  • Female
  • Fusion Regulatory Protein-1 / metabolism
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Large Neutral Amino Acid-Transporter 1 / genetics*
  • Large Neutral Amino Acid-Transporter 1 / metabolism
  • Male
  • Middle Aged
  • Multiple Myeloma / diagnosis
  • Multiple Myeloma / drug therapy
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / mortality
  • Neoplasm Staging
  • Prognosis
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Fusion Regulatory Protein-1
  • Large Neutral Amino Acid-Transporter 1