Overexpression of ATA1/SLC38A1 predicts future recurrence and death in Chinese patients with hilar cholangiocarcinoma

J Surg Res. 2011 Dec;171(2):663-8. doi: 10.1016/j.jss.2010.03.049. Epub 2010 Apr 18.

Abstract

System A amino acid transporter is a Na+-dependent active transport system, mediating the uptake of amino acids, dysregulation of which has been found to be associated with malignant transformation in mammalian cells. However, the role of ATA1 in hilar cholangiocarcinoma is unclear. Here, we investigated ATA1 expression and determined its clinical significance in hilar cholangiocarcinoma. Tissue microarray blocks containing tumor specimens obtained from 48 patients were constructed. Expression of ATA1 in these specimens was analyzed using immunohistochemical studies. ATA1 overexpression was observed in 22 cases (44.9%). Overexpression of ATA1 was significantly associated with lymph node metastases. ATA1 expression has a significant correlation with recurrence and poor survival in univariate analyses. Multivariate analyses revealed that ATA1 was an independent predictor for future recurrence in patients with cholangiocarcinoma. Increased expression of ATA1 is frequent in human hilar cholangiocarcinoma and significantly correlated with the progression of cholangiocarcinoma, suggesting the importance of ATA1 in cancer development and progression. ATA1 expression may be used to predict recurrence and death and can serve as a promising target for therapy of this malignancy.

MeSH terms

  • Adult
  • Amino Acid Transport System A / genetics*
  • Asian People / genetics
  • Asian People / statistics & numerical data
  • Bile Duct Neoplasms / genetics*
  • Bile Duct Neoplasms / mortality
  • Bile Duct Neoplasms / pathology
  • Bile Ducts, Intrahepatic*
  • Cholangiocarcinoma / genetics*
  • Cholangiocarcinoma / mortality
  • Cholangiocarcinoma / secondary
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / diagnosis
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / mortality
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • RNA, Messenger / metabolism

Substances

  • Amino Acid Transport System A
  • RNA, Messenger
  • SLC38A1 protein, human