Skip to main content
Erschienen in: Tumor Biology 5/2013

01.10.2013 | Research Article

The impact of L-type amino acid transporter 1 (LAT1) in human hepatocellular carcinoma

verfasst von: Juan Li, Juan Qiang, Shu-Fen Chen, Xin Wang, Jing Fu, Yao Chen

Erschienen in: Tumor Biology | Ausgabe 5/2013

Einloggen, um Zugang zu erhalten

Abstract

Upregulation of L-type amino acid transporter 1 (LAT1) has been reported to be associated with a poor prognosis in a variety of malignant tumors. However, the impact of LAT1 in hepatocellular carcinoma (HCC) remains unclear. The objective of this study was to investigate whether the expression of LAT1 in HCC was associated with established clinicopathological features. Quantitative reverse transcription polymerase chain reaction was used to detect LAT1 mRNA expression in 23 pairs of fresh-frozen HCC tissues and corresponding noncancerous tissues. Results showed that LAT1 mRNA expression level in HCC tissues was significantly higher than that in corresponding noncancerous tissues. To investigate the association between LAT1 protein expression and clinicopathological characteristics of HCC, immunohistochemistry was performed in 148 archived paraffin-embedded HCC samples. High LAT1 expression in HCC was associated significantly with tumor size (P = 0.032), histological differentiation (P = 0.003), and tumor stage (P = 0.01). Kaplan–Meier curves demonstrated that patients with a high expression of LAT1 have a significantly increased risk of shortened survival time. Moreover, stepwise Cox regression showed that LAT1 expression may be an independent prognostic factor. Collectively, our study demonstrated that LAT1was overexpressed in HCC and could be served as a potential prognostic marker.
Literatur
1.
3.
Zurück zum Zitat Bruix J, Sherman M, Practice Guidelines Committee, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma. Hepatology. 2005;42:1208–36. doi:10.1002/hep.20933.CrossRefPubMed Bruix J, Sherman M, Practice Guidelines Committee, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma. Hepatology. 2005;42:1208–36. doi:10.​1002/​hep.​20933.CrossRefPubMed
5.
Zurück zum Zitat Chen YJ, Yeh SH, Chen JT, Wu CC, Hsu MT, Tsai SF, et al. Chromosomal changes and clonality relationship between primary and recurrent hepatocellular carcinoma. Gastroenterology. 2000;119:431–40.CrossRefPubMed Chen YJ, Yeh SH, Chen JT, Wu CC, Hsu MT, Tsai SF, et al. Chromosomal changes and clonality relationship between primary and recurrent hepatocellular carcinoma. Gastroenterology. 2000;119:431–40.CrossRefPubMed
6.
Zurück zum Zitat Imamura H, Matsuyama Y, Tanaka E, Ohkubo T, Hasegawa K, Miyagawa S, et al. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol. 2003;38:200–7.CrossRefPubMed Imamura H, Matsuyama Y, Tanaka E, Ohkubo T, Hasegawa K, Miyagawa S, et al. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol. 2003;38:200–7.CrossRefPubMed
7.
Zurück zum Zitat Kühne A, Kaiser R, Schirmer M, Heider U, Muhlke S, Niere W, et al. Genetic polymorphisms in the amino acid transporters LAT1 and LAT2 in relation to the pharmacokinetics and side effects of melphalan. Pharmacogenet Genomics. 2007;17:505–17.CrossRefPubMed Kühne A, Kaiser R, Schirmer M, Heider U, Muhlke S, Niere W, et al. Genetic polymorphisms in the amino acid transporters LAT1 and LAT2 in relation to the pharmacokinetics and side effects of melphalan. Pharmacogenet Genomics. 2007;17:505–17.CrossRefPubMed
8.
Zurück zum Zitat Kanai Y, Segawa H, Miyamoto K, Uchino H, Takeda E, Endou H. Expression cloning and characterization of a transporter for large neutral amino acids activated by the heavy chain of 4F2 antigen (CD98). J Biol Chem. 1998;273:23629–32. doi:10.1074/jbc.273.37.23629.CrossRefPubMed Kanai Y, Segawa H, Miyamoto K, Uchino H, Takeda E, Endou H. Expression cloning and characterization of a transporter for large neutral amino acids activated by the heavy chain of 4F2 antigen (CD98). J Biol Chem. 1998;273:23629–32. doi:10.​1074/​jbc.​273.​37.​23629.CrossRefPubMed
9.
Zurück zum Zitat Yanagida O, Kanai Y, Chairoungdua A, Kim DK, Segawa H, Nii T, et al. Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines. Biochim Biophys Acta. 2001;1514:291–302.CrossRefPubMed Yanagida O, Kanai Y, Chairoungdua A, Kim DK, Segawa H, Nii T, et al. Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines. Biochim Biophys Acta. 2001;1514:291–302.CrossRefPubMed
11.
Zurück zum Zitat Kobayashi H, Ishii Y, Takayama T. Expression of L-type amino acid transporter 1 (LAT1) in esophageal carcinoma. J Surg Oncol. 2005;90:233–8.CrossRefPubMed Kobayashi H, Ishii Y, Takayama T. Expression of L-type amino acid transporter 1 (LAT1) in esophageal carcinoma. J Surg Oncol. 2005;90:233–8.CrossRefPubMed
12.
Zurück zum Zitat Imai H, Kaira K, Oriuchi N, Shimizu K, Tominaga H, Yanagitani N, et al. Inhibition of L-type amino acid transporter 1 has antitumor activity in non-small cell lung cancer. Anticancer Res. 2010;30:4819–28.PubMed Imai H, Kaira K, Oriuchi N, Shimizu K, Tominaga H, Yanagitani N, et al. Inhibition of L-type amino acid transporter 1 has antitumor activity in non-small cell lung cancer. Anticancer Res. 2010;30:4819–28.PubMed
14.
Zurück zum Zitat Nakanishi K, Ogata S, Matsuo H, Kanai Y, Endou H, Hiroi S, et al. Expression of LAT1 predicts risk of progression of transitional cell carcinoma of the upper urinary tract. Virchows Arch. 2007;451:681–90.CrossRefPubMed Nakanishi K, Ogata S, Matsuo H, Kanai Y, Endou H, Hiroi S, et al. Expression of LAT1 predicts risk of progression of transitional cell carcinoma of the upper urinary tract. Virchows Arch. 2007;451:681–90.CrossRefPubMed
15.
16.
Zurück zum Zitat Ebara T, Kaira K, Saito J, Shioya M, Asao T, Takahashi T, et al. L-type amino-acid transporter 1 expression predicts the response to preoperative hyperthermo-chemoradiotherapy for advanced rectal cancer. Anticancer Res. 2010;30:4223–7.PubMed Ebara T, Kaira K, Saito J, Shioya M, Asao T, Takahashi T, et al. L-type amino-acid transporter 1 expression predicts the response to preoperative hyperthermo-chemoradiotherapy for advanced rectal cancer. Anticancer Res. 2010;30:4223–7.PubMed
17.
Zurück zum Zitat Kaira K, Oriuchi N, Takahashi T, Nakagawa K, Ohde Y, Okumura T, et al. L-type amino acid transporter 1 (LAT1) expression in malignant pleural mesothelioma. Anticancer Res. 2011;31:4075–82.PubMed Kaira K, Oriuchi N, Takahashi T, Nakagawa K, Ohde Y, Okumura T, et al. L-type amino acid transporter 1 (LAT1) expression in malignant pleural mesothelioma. Anticancer Res. 2011;31:4075–82.PubMed
18.
Zurück zum Zitat Yanagisawa N, Ichinoe M, Mikami T, Nakada N, Hana K, Koizumi W, et al. High expression of L-type amino acid transporter 1 (LAT1) predicts poor prognosis in pancreatic ductal adenocarcinomas. J Clin Pathol. 2012 Nov;65(11):1019–23. doi:10.1136/jclinpath-2012-200826. Yanagisawa N, Ichinoe M, Mikami T, Nakada N, Hana K, Koizumi W, et al. High expression of L-type amino acid transporter 1 (LAT1) predicts poor prognosis in pancreatic ductal adenocarcinomas. J Clin Pathol. 2012 Nov;65(11):1019–23. doi:10.​1136/​jclinpath-2012-200826.
20.
Zurück zum Zitat Sobin LH, Wittekind CL. TNM classification of malignant tumors. New York: John Wiley & Sons; 2002. Sobin LH, Wittekind CL. TNM classification of malignant tumors. New York: John Wiley & Sons; 2002.
22.
Zurück zum Zitat Liu Z, Li L, Yang Z, Luo W, Li X, Yang H, et al. Increased expression of MMP9 is correlated with poor prognosis of nasopharyngeal carcinoma. BMC Cancer. 2010;10:270.PubMedCentralCrossRefPubMed Liu Z, Li L, Yang Z, Luo W, Li X, Yang H, et al. Increased expression of MMP9 is correlated with poor prognosis of nasopharyngeal carcinoma. BMC Cancer. 2010;10:270.PubMedCentralCrossRefPubMed
Metadaten
Titel
The impact of L-type amino acid transporter 1 (LAT1) in human hepatocellular carcinoma
verfasst von
Juan Li
Juan Qiang
Shu-Fen Chen
Xin Wang
Jing Fu
Yao Chen
Publikationsdatum
01.10.2013
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 5/2013
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-0861-5

Weitere Artikel der Ausgabe 5/2013

Tumor Biology 5/2013 Zur Ausgabe

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

CUP-Syndrom: Künstliche Intelligenz kann Primärtumor finden

30.04.2024 Künstliche Intelligenz Nachrichten

Krebserkrankungen unbekannten Ursprungs (CUP) sind eine diagnostische Herausforderung. KI-Systeme können Pathologen dabei unterstützen, zytologische Bilder zu interpretieren, um den Primärtumor zu lokalisieren.

Sind Frauen die fähigeren Ärzte?

30.04.2024 Gendermedizin Nachrichten

Patienten, die von Ärztinnen behandelt werden, dürfen offenbar auf bessere Therapieergebnisse hoffen als Patienten von Ärzten. Besonders gilt das offenbar für weibliche Kranke, wie eine Studie zeigt.

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.