Relationship between LAT1 expression and response to platinum-based chemotherapy in non-small cell lung cancer patients with postoperative recurrence

Anticancer Res. 2011 Nov;31(11):3775-82.

Abstract

Background: The aim of this study was to investigate whether L-type amino acid transporter 1 (LAT1) expression can predict poor outcome after chemotherapy in patients with non-small cell lung cancer (NSCLC).

Materials and methods: Immunohistochemistry was carried out to examine the expression of LAT1, CD98, vascular endothelial growth factor (VEGF), Ki-67, phosphorylation of Akt (p-Akt), phosphorylation of mammalian target of rapamycin (p-mTOR) and p53 in resected lung tumor specimens obtained from 56 patients treated with platinum-based chemotherapy.

Results: Positive LAT1 and CD98 expression was recognized in 45% (25/56) and 34% (19/56), respectively. In NSCLC (N=56), LAT1, CD98, VEGF, Ki-67 and p53 were significant factors for predicting poor outcome, and adenocarcinoma was an independent factor for predicting favorable prognosis. LAT1 expression was closely associated with chemoresistance. In adenocarcinoma (N=37), a statistically significant inverse relationship was observed between the expression of LAT1, VEGF and Ki-67 and epidermal growth factor receptor (EGFR) mutation, and positive expression of LAT1 and VEGF was an independent factor for predicting poor prognosis after chemotherapy.

Conclusion: LAT1 expression may be useful for predicting response and outcome after systemic chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / therapy
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Combined Modality Therapy
  • Female
  • Fusion Regulatory Protein-1 / metabolism
  • Humans
  • Immunoenzyme Techniques
  • Ki-67 Antigen / metabolism
  • Large Neutral Amino Acid-Transporter 1 / metabolism*
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / therapy
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local / metabolism*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / therapy
  • Organoplatinum Compounds / administration & dosage
  • Prognosis
  • Survival Rate
  • TOR Serine-Threonine Kinases / metabolism
  • Tumor Suppressor Protein p53 / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Biomarkers, Tumor
  • Fusion Regulatory Protein-1
  • Ki-67 Antigen
  • Large Neutral Amino Acid-Transporter 1
  • Organoplatinum Compounds
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • MTOR protein, human
  • TOR Serine-Threonine Kinases