CPA4 is a Novel Diagnostic and Prognostic Marker for Human Non-Small-Cell Lung Cancer

Background. Carboxypeptidase A4 (CPA4) belongs to a member of the metallocarboxypeptidase family, and its expression in lung cancer samples and clinical significance are still not investigated until now. In this study, we aimed to evaluate the level of CPA4 in non-small-cell lung cancer (NSCLC) samples and correlate its level with clinical outcome. Methods. CPA4 gene expression in lung cancer tissues were analyzed by using the Oncomine database (www.oncomine.org). The expression of CPA4, Survivin and VEGF in lung cancer and adjacent normal tissues were evaluated by IHC using the corresponding primary antibodies on two different commercial tissue arrays (Shanghai Biochip Co., Ltd., Shanghai, China). Their levels in serum were determined by using commercial human enzyme-linked immunosorbent assay kits. We also examined their relations to clinicopathologic parameters, and explored the diagnostic and prognostic value in NSCLC. Results. We identified an elevation of CPA4 in mRNA level and gene amplification in lung cancer tissues in comparison to normal lung tissues. High CPA4 expression was observed in 120/165 (72.7%) NSCLC samples, and significantly correlated with Tumor size, Depth of invasion, Lymph Node Metastasis, Stage, VEGF level and Survivin level. High CPA4 expression is associated with poor prognosis of NSCLC patients. Multivariable Cox regression analysis demonstrated that CPA4 expression was an independent prognostic factor. Furthermore, serum CPA4 level was also significantly higher in NSCLC patients than in healthy controls. Logistic regression analysis revealed that serum CPA4 and CYFRA21-1 level were the significant parameters for detecting NSCLC. Receiver operating characteristic curves (ROC) in NSCLC patients versus normal people yielded the optimal cut-off value was 2.70 ng/ml for CPA4 and 19 ng/ml for CYFRA21-1, respectively. The area under ROC curve (AUC) was 0.830 for the combination of the two tumor markers. Conclusion. Our results demonstrated that overexpression of CPA4 in NSCLC is associated with an unfavorable prognosis, and serum CPA4 level combining with serum CYFRA21-1 level could be used to aid early detection of NSCLC.