Isoda Atsushi, Kaira Kyoichi, Iwashina Masanori, Oriuchi Noboru, Tominaga Hideyuki, Nagamori Shushi, Kanai Yoshikatsu, Oyama Tetsunari, Asao Takayuki, Matsumoto Morio, Sawamura Morio
Department of Hematology, National Hospital Organization Nishigunma Hospital, Gunma, Japan.
Cancer Sci. 2014 Nov;105(11):1496-502. doi: 10.1111/cas.12529. Epub 2014 Oct 9.
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.
L型氨基酸转运体1(LAT1)在细胞生长和存活中起关键作用。为了确定LAT1在多发性骨髓瘤(MM)中的预后意义,我们通过免疫组织化学方法研究了100例新诊断MM患者骨髓瘤细胞上LAT1及其功能亚基4Fc重链(CD98)的表达情况。分别在56%和45%的患者中检测到LAT1和CD98的高表达(中度或强染色强度)。LAT1表达评分与Ki-67指数呈正相关(r = 0.631,P < 0.001),LAT1高表达和低表达患者之间的Durie-Salmon分期存在统计学显著差异(P = 0.03)。在43例接受美法仑和泼尼松治疗的患者中,LAT1高表达组的总缓解率(60.0%)显著高于LAT1低表达组(17.6%)(P = 0.03)。多变量分析证实,LAT1高表达是独立于国际分期系统预测总体生存不良的显著预后因素(P均 = 0.01)。在此,我们表明LAT1的过表达与新诊断MM患者的高增殖和不良预后显著相关。因此,LAT1可能是识别高危MM的一个有前景的病理标志物。