Prognostic significance of amino-acid transporter expression (LAT1, ASCT2, and xCT) in surgically resected tongue cancer

Br J Cancer. 2014 May 13;110(10):2506-13. doi: 10.1038/bjc.2014.178. Epub 2014 Apr 24.

Abstract

Background: Amino-acid transporters are necessary for the tumour cell growth and survival, and have a crucial role in the development and invasiveness of cancer cells. But, it remains unclear about the prognostic significance of L-type amino-acid transporter 1 (LAT1), system ASC amino-acid transporter-2 (ASCT2), and xCT expression in patients with tongue cancer. We conducted the clinicopathological study to investigate the protein expression of these amino-acid transporters in tongue cancer.

Methods: Eighty-five patients with surgically resected tongue cancer were evaluated. Tumour sections were stained by immunohistochemistry for LAT1, ASCT2, xCT, 4F2hc/CD98hc (4F2hc), Ki-67, and microvessel density (MVD) determined by CD34, and p53.

Results: L-type amino-acid transporter 1 and 4F2hc were highly expressed in 61% (52 out of 85) and 45% (38 out of 47), respectively. ASC amino-acid transporter-2 and xCT were positively expressed in 59% (50 out of 85) and 21% (18 out of 85), respectively. The expression of both LAT1 and ASCT2 was significantly associated with disease staging, lymph-node metastasis, lymphatic permeation, 4F2hc expression and cell proliferation (Ki-67). xCT expression indicated a significant association with advanced stage and tumour factor. By univariate analysis, disease staging, lymphatic permeation, vascular invasion, LAT1, ASCT2, 4F2hc, and Ki-67 had a significant relationship with overall survival. Multivariate analysis confirmed that LAT1 was an independent prognostic factor for predicting poor prognosis.

Conclusions: L-type amino-acid transporter 1 and ASCT2 can serve as a significant prognostic factor for predicting worse outcome after surgical treatment and may have an important role in the development and aggressiveness of tongue cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amino Acid Transport System ASC / analysis*
  • Amino Acid Transport System y+ / analysis*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Squamous Cell / blood supply
  • Carcinoma, Squamous Cell / chemistry*
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / surgery
  • Chemotherapy, Adjuvant
  • Combined Modality Therapy
  • Disease-Free Survival
  • Docetaxel
  • Drug Combinations
  • Female
  • Fusion Regulatory Protein 1, Heavy Chain / analysis
  • Humans
  • Kaplan-Meier Estimate
  • Ki-67 Antigen / analysis
  • Large Neutral Amino Acid-Transporter 1 / analysis*
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Minor Histocompatibility Antigens
  • Neoplasm Proteins / analysis*
  • Neoplasm Staging
  • Oxonic Acid / administration & dosage
  • Prognosis
  • Taxoids / administration & dosage
  • Tegafur / administration & dosage
  • Tongue Neoplasms / blood supply
  • Tongue Neoplasms / chemistry*
  • Tongue Neoplasms / drug therapy
  • Tongue Neoplasms / surgery
  • Treatment Outcome
  • Tumor Suppressor Protein p53 / analysis

Substances

  • Amino Acid Transport System ASC
  • Amino Acid Transport System y+
  • Biomarkers, Tumor
  • Drug Combinations
  • Fusion Regulatory Protein 1, Heavy Chain
  • Ki-67 Antigen
  • Large Neutral Amino Acid-Transporter 1
  • Minor Histocompatibility Antigens
  • Neoplasm Proteins
  • SLC1A5 protein, human
  • SLC3A2 protein, human
  • SLC7A11 protein, human
  • TP53 protein, human
  • Taxoids
  • Tumor Suppressor Protein p53
  • S 1 (combination)
  • Tegafur
  • Docetaxel
  • Oxonic Acid