Namikawa Masashi, Kakizaki Satoru, Kaira Kyoichi, Tojima Hiroki, Yamazaki Yuichi, Horiguchi Norio, Sato Ken, Oriuchi Noboru, Tominaga Hideyuki, Sunose Yutaka, Nagamori Shushi, Kanai Yoshikatsu, Oyama Tetsunari, Takeyoshi Izumi, Yamada Masanobu
Department of Medicine and Molecular Science, Gunma University, Gunma, Japan.
Department of Internal Medicine, Kiryu Kosei General Hospital, Kiryu, Japan.
Hepatol Res. 2015 Sep;45(9):1014-1022. doi: 10.1111/hepr.12431. Epub 2014 Dec 11.
Amino acid transporters play an important role in tumor progression and survival of cancer cells. However, the prognostic significance of L-type amino acid transporter 1 (LAT1), system ASC amino acid transporter-2 (ASCT2) and xCT expression in patients with hepatocellular carcinoma (HCC) remains unclear. The aim of this study is to investigate the clinicopathological significance of these amino acid transporters in patients with HCC.
We examined 84 patients with surgically resected HCC. Tumor sections were stained by immunohistochemistry for LAT1, ASCT2, xCT, 4F2hc/CD98hc (4F2hc), Ki-67 and microvessel density (MVD) determined by CD34.
LAT1, 4F2hc, ASCT2 and xCT were positively expressed in 61% (50/84), 77% (65/84), 63% (53/84) and 65% (55/84), respectively. Positive LAT1 expression was significantly associated with 4F2hc expression, Ki-67 and the serum albumin. By univariate analysis, LAT1 expression, disease stage and albumin had a significant relationship with overall survival. Tumor size, disease stage, portal vein invasion, albumin and α-fetoprotein had a significant relationship with progression-free survival. Multivariate analysis confirmed that LAT1 expression is an independent and significant prognostic factor for predicting worse outcome after surgery.
LAT1 can serve as a significant prognostic marker for predicting negative prognosis after surgery.
氨基酸转运体在肿瘤进展及癌细胞存活中发挥重要作用。然而，L型氨基酸转运体1（LAT1）、系统ASC氨基酸转运体-2（ASCT2）及xCT在肝细胞癌（HCC）患者中的预后意义仍不明确。本研究旨在探讨这些氨基酸转运体在HCC患者中的临床病理意义。
我们对84例接受手术切除的HCC患者进行了研究。肿瘤切片采用免疫组织化学法检测LAT1、ASCT2、xCT、4F2hc/CD98hc（4F2hc）、Ki-67，并通过CD34测定微血管密度（MVD）。
LAT1、4F2hc、ASCT2及xCT的阳性表达率分别为61%（50/84）、77%（65/84）、63%（53/84）及65%（55/84）。LAT1阳性表达与4F2hc表达、Ki-67及血清白蛋白显著相关。单因素分析显示，LAT1表达、疾病分期及白蛋白与总生存期显著相关。肿瘤大小、疾病分期、门静脉侵犯、白蛋白及甲胎蛋白与无进展生存期显著相关。多因素分析证实，LAT1表达是预测术后不良预后的独立且显著的预后因素。
LAT1可作为预测术后不良预后的重要预后标志物。
