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Circulating Aminopeptidase N/CD13 Is an Independent Prognostic Factor in Patients with Non–Small Cell Lung Cancer

Authors' Affiliations: ¹ Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan and ² The Fifth Department of Oncology and Department of Thoracic Surgery, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka, Japan

Requests for reprints: Akihito Yokoyama, Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima 734-8551, Japan. Phone: 81-82-257-5196; Fax: 81-82-255-7360; E-mail: yokoyan{at}hiroshima-u.ac.jp.

Purpose: Aminopeptidase N, also known as CD13, has important roles in tumor metastasis and angiogenesis. Its expression in tumor tissue has been reported to be associated with poor prognosis. However, the clinical significance of circulating aminopeptidase N/CD13 in patients with solid tumors is unknown. We previously developed an aminopeptidase N/CD13–specific monoclonal antibody (mAb) MH8-11, which inhibits cell motility and angiogenesis in vitro. The aim of this study was to evaluate the clinical significance of circulating aminopeptidase N/CD13 protein detected by mAb MH8-11 in patients with non–small cell lung cancer (NSCLC).

Experimental Design: We used electrochemiluminescence immunoassay with mAb MH8-11 to determine circulating aminopeptidase N/CD13 levels in 90 healthy volunteers and 90 patients with NSCLC. Circulating aminopeptidase N/CD13 levels were measured in sera taken before treatment and evaluated for a relationship with clinical outcomes.

Results: A significant correlation was found between tumor progression and serum aminopeptidase N/CD13 concentrations (r = 0.23, P = 0.029). High serum aminopeptidase N/CD13 levels (n = 17) were associated with advanced stage (P = 0.004) or poor performance status (P = 0.001). The overall survival rate for patients with high serum aminopeptidase N/CD13 levels (n = 17) was significantly less than that of patients with low serum aminopeptidase N/CD13 levels (n = 73, P < 0.0001). In a multivariate survival analysis in patients with NSCLC, serum aminopeptidase N/CD13 levels had an independent influence on survival (relative risk, 4.1; 95% confidence interval, 1.9-8.8).

Conclusions: Our data suggest that a high level of circulating aminopeptidase N/CD13 at diagnosis is an independent prognostic factor in patients with NSCLC.