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

Cancer Science

Atsushi Isoda⁶  Kyoichi Kaira¹  Masanori Iwashina²  Noboru Oriuchi⁴  Hideyuki Tominaga⁷  Shushi Nagamori⁵  Yoshikatsu Kanai⁵  Tetsunari Oyama³  Takayuki Asao¹  Morio Matsumoto⁶ 

[1] Department of Oncology Clinical Development, Gunma University Graduate School of Medicine, Gunma, Japan;Department of Clinical Laboratory, National Hospital Organization Nishigunma Hospital, Gunma, Japan;Department of Diagnostic Pathology, Gunma University Graduate School of Medicine, Gunma, Japan;Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Gunma, Japan;Division of Bio-System Pharmacology, Osaka University Graduate School of Medicine, Osaka, Japan;Department of Hematology, National Hospital Organization Nishigunma Hospital, Gunma, Japan;Advanced Clinical Research Center, Fukushima Medical University, Fukushima, Japan

关键词: CD98;    L‐type amino‐acid transporter 1;    melphalan;    multiple myeloma;    prognosis;   

DOI  :  10.1111/cas.12529

来源: Wiley

【 摘 要 】

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.

【 授权许可】

CC BY-NC   
© 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

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