CPA4 is a Novel Diagnostic and Prognostic Marker for Human Non-Small-Cell Lung Cancer.
CPA4 is a Novel Diagnostic and Prognostic Marker for Human Non-Small-Cell Lung Cancer.
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CPA4是人类非小细胞肺癌的新型诊断和预后标记。
DOI：
10.7150/jca.15209
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发表时间：
2016
影响因子：
3.9
通讯作者：
Sun D
中科院分区：
文献类型：
--
作者：
Sun L;Wang Y;Yuan H;Burnett J;Pan J;Yang Z;Ran Y;Myers I;Sun D
背景。羧肽酶A4（CPA4）属于金属羧肽酶家族的一员，其在肺癌样本中的表达及临床意义至今尚未得到研究。在本研究中，我们旨在评估非小细胞肺癌（NSCLC）样本中CPA4的水平，并将其水平与临床结果相关联。
方法。利用Oncomine数据库（www.oncomine.org）分析肺癌组织中CPA4基因的表达。使用相应的一抗在两种不同的商业组织芯片（上海生物芯片有限公司，中国上海）上通过免疫组化评估肺癌及邻近正常组织中CPA4、生存素（Survivin）和血管内皮生长因子（VEGF）的表达。使用商业人酶联免疫吸附测定试剂盒测定它们在血清中的水平。我们还检查了它们与临床病理参数的关系，并探讨了在NSCLC中的诊断和预后价值。
结果。我们发现与正常肺组织相比，肺癌组织中CPA4在mRNA水平升高且基因扩增。在165例NSCLC样本中有120例（72.7%）观察到CPA4高表达，且与肿瘤大小、浸润深度、淋巴结转移、分期、VEGF水平和Survivin水平显著相关。CPA4高表达与NSCLC患者预后不良相关。多变量Cox回归分析表明CPA4表达是一个独立的预后因素。此外，NSCLC患者的血清CPA4水平也显著高于健康对照组。逻辑回归分析显示血清CPA4和CYFRA21 - 1水平是检测NSCLC的重要参数。NSCLC患者与正常人的受试者工作特征曲线（ROC）得出CPA4的最佳截断值为2.70 ng/ml，CYFRA21 - 1为19 ng/ml。两种肿瘤标志物联合的ROC曲线下面积（AUC）为0.830。
结论。我们的结果表明，NSCLC中CPA4的过表达与不良预后相关，血清CPA4水平结合血清CYFRA21 - 1水平可用于辅助NSCLC的早期检测。
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.