Expression Of Aminopeptidase N/CD13 And Its Clinical Significance In Non-small Cell Lung Cancer

Background: Aminopeptidase N (CD13) is a widely expressed ectoenzyme with functions including extracellular matrix degradation,cell migration,angiogenesis,tumor invasion and other pathophysiological processes. In the hematopoietic compartment, the APN/CD13 metalloprotease is one of the earliest markers of cells committed to the myeloid lineage where it is expressed exclusively on the surface of myeloid progenitors and their differentiated progeny. APN/CD13 is also found in nonhematopoietic tissues such as the brush border of the small intestine, proximal renal tubules,breast tissue,secretory epithelium of bronchial glands,colonic mucosa and the membrane of cells in the central nervous system. In many malignant tissues, such as esophageal cancer,pancreatic carcinoma and gastric cancer,a high level APN/CD13 expression has been reported. These researches indicated that the APN/CD13 expression in many malignant tissues has important clinic significance. At the same time,some randomized controlled studies of APN/CD13 inhibitor are performed in bladder carcinoma,non-small cell lung cancer and gastric cancer. Part of studies told us APN/CD13 inhibitor therapy could prolong survival time. In this experiment we studied the expression of APN/CD13 and the relationship between APN/CD13 expression and clinical features and the prognosis of patients in non-small cell lung cancer.Methods: We investigated the expression of APN/CD13 in 160 patients with resected non-small cell lung cancer (NSCLC), 50 corresponding normal tissues, and 40 nonmalignant tissues by immunohistochemical analysis,using anti-CD13 monoclonal antibody.Results: APN/CD13 protein was mainly found in the cell membrane of tumor cells in human lung adenocarcinoma , but in the cell membrane of interstitial tissue in human lung squamous cancer. APN/CD13 was also observed in the basement membrane of the bronchial epithelium,secretory epithelium of bronchial glands and macrophages in the corresponding normal tissues and nonmalignant tissues. APN/CD13 protein was positive by immunohistochemistry in 62.5% (55 of 88) of lung squamous cancer and 50% (36 of 72) of lung adenocarcinoma. There was no relationship between the APN/CD13 expression and clinicopathologic features, such as age, gender, smoking ,TNM stage, tumor size and histological type in lung adenocarcinoma, but in human lung squamous cancer we can find the relationship between the APN/CD13 expression and age(P=0.036) and nodal status(P=0.003). Analyzing the effect of expression of APN/CD13 on survival of 160 NSCLC patients, the Kaplan-Meier survival curves show that the patients with high expression of APN/CD13 have a poor survival rate, and the relationship between the survival rate and expression of APN/CD13 was statistically significant (P<0.001). Then by using stepwise Cox proportional hazard regression testing, expression of APN/CD13 was an independently factor affecting the patients'surviva(lRR=2.710,95%CI=1.564-4.694,P<0.001).Conclusion: Our data suggested that APN/CD13 may be an useful prognostic marker for patients with non-small cell lung cancer.