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

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.

• Authors: M Toyoda, K Kaira, Y Ohshima, N S Ishioka, M Shino, K Sakakura, Y Takayasu, K Takahashi, H Tominaga, N Oriuchi, S Nagamori, Y Kanai, T Oyama, K Chikamatsu
• Journal: British journal of cancer (Br J Cancer) Vol. 110 Issue 10 Pg. 2506-13 (May 13 2014) ISSN: 1532-1827 [Electronic] England
• PMID: 24762957 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• 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, chemistry, drug therapy, 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, chemistry, drug therapy, surgery)
• Treatment Outcome
• Tumor Suppressor Protein p53 (analysis)