Clinical significance of aminopeptidase N in non-small cell lung cancer

Clin Cancer Res. 2006 Jul 1;12(13):3971-8. doi: 10.1158/1078-0432.CCR-06-0338.

Abstract

Purpose: The aim of our study is to investigate the mechanism of metastasis, to detect novel metastasis-associated molecules, and to evaluate the molecules from the point of view of clinical application. A monoclonal antibody MH8-11, which we established, recognizes a glycoprotein that is identical to aminopeptidase N (APN/CD13). APN/CD13 degrades the extracellular matrix, while it is also involved in cell motility and improves angiogenesis.

Experimental design: We investigated the expression of APN/CD13 in 194 cases of non-small cell lung cancer (NSCLC) by immunohistochemical analyses and reverse transcription-PCR assay to determine the significance of this prognostic factor; 95 tumors were stage I, 36 were stage II, 39 were stage IIIA, and 24 were stage IIIB. Moreover, we investigated that the relationship between the expression of APN/CD13 and angiogenesis and prognosis for patients with NSCLC.

Results: We found a correlation between the expression of APN/CD13 and angiogenesis (r = 0.659; P < 0.0001). In the 194 patients with NSCLC, we found 68 patients to be APN/CD13+ and 126 patients to be APN/CD13-. The 5-year survival rate in patients with APN/CD13+ tumors was significantly lower than in those whose tumors had negative APN/CD13 (48.3% versus 67.1%; P = 0.0001).

Conclusion: Our data suggest the expression of APN/CD13 for patients with NSCLC to be associated with a poor prognosis and angiogenesis. This is the first study to show the relationship between the expression of APN/CD13 and the prognosis of patients with NSCLC. The inhibition of APN/CD13 may be an effective new molecular target therapy for patients with NSCLC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • CD13 Antigens* / analysis
  • CD13 Antigens* / genetics
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / enzymology*
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Cell Line, Tumor
  • Female
  • Flow Cytometry / methods
  • Gene Expression Profiling
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neovascularization, Pathologic / diagnosis
  • Neovascularization, Pathologic / enzymology
  • Prognosis
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Survival Rate

Substances

  • CD13 Antigens