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

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

Research output: Contribution to journal › Article › peer-review

49 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1014-1022
Number of pages	9
Journal	Hepatology Research
Volume	45
Issue number	9
DOIs	https://doi.org/10.1111/hepr.12431
Publication status	Published - 01-09-2015
Externally published	Yes

All Science Journal Classification (ASJC) codes

Hepatology
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/hepr.12431

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Namikawa, M., Kakizaki, S., Kaira, K., Tojima, H., Yamazaki, Y., Horiguchi, N., Sato, K., Oriuchi, N., Tominaga, H., Sunose, Y., Nagamori, S., Kanai, Y., Oyama, T., Takeyoshi, I., & Yamada, M. (2015). Expression of amino acid transporters (LAT1, ASCT2 and xCT) as clinical significance in hepatocellular carcinoma. Hepatology Research, 45(9), 1014-1022. https://doi.org/10.1111/hepr.12431

@article{a64fdd1a1c624964a56f6fee7c608847,

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

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, Hepatocellular carcinoma, LAT1, Prognostic factor, xCT",

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

note = "Publisher Copyright: {\textcopyright} 2015 John Wiley \& Sons, Ltd.",

year = "2015",

month = sep,

day = "1",

doi = "10.1111/hepr.12431",

language = "English",

volume = "45",

pages = "1014--1022",

journal = "Hepatology Research",

issn = "1386-6346",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "9",

}

Namikawa, M, Kakizaki, S, Kaira, K, Tojima, H, Yamazaki, Y, Horiguchi, N, Sato, K, Oriuchi, N, Tominaga, H, Sunose, Y, Nagamori, S, Kanai, Y, Oyama, T, Takeyoshi, I & Yamada, M 2015, 'Expression of amino acid transporters (LAT1, ASCT2 and xCT) as clinical significance in hepatocellular carcinoma', Hepatology Research, vol. 45, no. 9, pp. 1014-1022. https://doi.org/10.1111/hepr.12431

TY - JOUR

T1 - Expression of amino acid transporters (LAT1, ASCT2 and xCT) as clinical significance in hepatocellular carcinoma

AU - Namikawa, Masashi

AU - Kakizaki, Satoru

AU - Kaira, Kyoichi

AU - Tojima, Hiroki

AU - Yamazaki, Yuichi

AU - Horiguchi, Norio

AU - Sato, Ken

AU - Oriuchi, Noboru

AU - Tominaga, Hideyuki

AU - Sunose, Yutaka

AU - Nagamori, Shushi

AU - Kanai, Yoshikatsu

AU - Oyama, Tetsunari

AU - Takeyoshi, Izumi

AU - Yamada, Masanobu

PY - 2015/9/1

Y1 - 2015/9/1

N2 - 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.

AB - 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.

KW - ASCT2

KW - Hepatocellular carcinoma

KW - LAT1

KW - Prognostic factor

KW - xCT

UR - https://www.scopus.com/pages/publications/84941024079

UR - https://www.scopus.com/pages/publications/84941024079#tab=citedBy

U2 - 10.1111/hepr.12431

DO - 10.1111/hepr.12431

M3 - Article

AN - SCOPUS:84941024079

SN - 1386-6346

VL - 45

SP - 1014

EP - 1022

JO - Hepatology Research

JF - Hepatology Research

IS - 9

ER -

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

Abstract

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