Clinical significance of l-type amino acid transporter 1 expression as a prognostic marker and potential of new targeting therapy in tongue cancer

舌癌におけるL型アミノ酸トランスポーター1発現の予後マーカーとしての臨床的意義と新規標的治療の可能性について

解良 恭一*; 豊田 実*; 大島 康宏; 織内 昇*; 金井 好克*; 小山 徹也*; 山田 正信*; 浅尾 高行*; 近松 一朗*

Kaira, Kyoichi*; Toyoda, Minoru*; Ohshima, Yasuhiro; Oriuchi, Noboru*; Kanai, Yoshikatsu*; Oyama, Tetsunari*; Yamada, Masanobu*; Asao, Takayuki*; Chikamatsu, Kazuaki*

This study was conducted to determine biological significance of L-type amino acid transporter 1 (LAT1) expression and investigate whether LAT1 could be a prognostic biomarker for tongue cancer. Eighty-five patients with surgically resected tongue cancer were evaluated. Tumor sections were stained by immunohistochemistry for LAT1, ASCT2, xCT, CD98, CD147, Ki-67, microvessel density determined by CD34, and p53. Biological significance of LAT1 expression was investigated by experiments with LAT inhibitor, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) using tongue cell line. LAT1, ASCT2, xCT, CD98 and CD147 were highly expressed in 61%, 59%, 21%, 45% and 33%, respectively. The expression of LAT1 was significantly associated with disease staging, lymph node metastasis, lymphatic permeation, cell proliferation (Ki-67), and the expression level of CD98, ASCT2 and CD147 as amino acid transporter complexes. Multivariate analysis confirmed that LAT1 was an independent prognostic factor for predicting poor prognosis. preliminary experiment indicated that BCH significantly suppressed growth of the tumor and yielded an additive therapeutic efficacy to cisplatin. These rusults suggests that LAT1 can serve as a promising pathological marker to predict the outcome in patients with tongue cancer. Inhibition of LAT1 may be an effective targeted therapy for this distressing disease.