Masashi Namikawa1,2, Satoru Kakizaki1, Kyoichi Kaira1,3, Hiroki Tojima1, Yuichi Yamazaki1, Norio Horiguchi1, Ken Sato1, Noboru Oriuchi4, Hideyuki Tominaga5, Yutaka Sunose6, Shushi Nagamori7, Yoshikatsu Kanai7, Tetsunari Oyama8, Izumi Takeyoshi6, Masanobu Yamada1. 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.
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.
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.