Expression of amino acid transporters (LAT1, ASCT2 and xCT) as clinical significance in hepatocellular carcinoma

Masashi Namikawa; Satoru Kakizaki; Kyoichi Kaira; Hiroki Tojima; Yuichi Yamazaki; Norio Horiguchi; Ken Sato; Noboru Oriuchi; Hideyuki Tominaga; Yutaka Sunose; Shushi Nagamori; Yoshikatsu Kanai; Tetsunari Oyama; Izumi Takeyoshi; Masanobu Yamada

doi:10.1111/hepr.12431

Expression of amino acid transporters (LAT1, ASCT2 and xCT) as clinical significance in hepatocellular carcinoma

Hepatol Res. 2015 Sep;45(9):1014-1022. doi: 10.1111/hepr.12431. Epub 2014 Dec 11.

Authors

Masashi Namikawa^{1

2}, Satoru Kakizaki¹, Kyoichi Kaira^{1

3}, Hiroki Tojima¹, Yuichi Yamazaki¹, Norio Horiguchi¹, Ken Sato¹, Noboru Oriuchi⁴, Hideyuki Tominaga⁵, Yutaka Sunose⁶, Shushi Nagamori⁷, Yoshikatsu Kanai⁷, Tetsunari Oyama⁸, Izumi Takeyoshi⁶, Masanobu Yamada¹

Affiliations

¹ Department of Medicine and Molecular Science, Gunma University, Gunma, Japan.
² Department of Internal Medicine, Kiryu Kosei General Hospital, Kiryu, Japan.
³ Department of Oncology Clinical Development, Gunma University, Gunma, Japan.
⁴ Department of Diagnostic Radiology and Nuclear Medicine, Gunma University, Gunma, Japan.
⁵ Advanced Clinical Research Center, Fukushima Medical University, Fukushima, Japan.
⁶ Department of Thoracic and Visceral Surgery, Gunma University, Gunma, Japan.
⁷ Division of Bio-system Pharmacology, Graduate School of Medicine, Osaka University, Osaka, Japan.
⁸ Department of Diagnostic Pathology, Graduate School of Medicine, Gunma University, Gunma, Japan.

PMID: 25297701
DOI: 10.1111/hepr.12431

Abstract

Aim: 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.

Methods: 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.

Results: 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.

Conclusion: LAT1 can serve as a significant prognostic marker for predicting negative prognosis after surgery.

Keywords: ASCT2; LAT1; hepatocellular carcinoma; prognostic factor; xCT.