Nesterova Maria V, Johnson Natalie, Cheadle Christopher, Bates Susan E, Mani Sridhar, Stratakis Constantine A, Khan Islam U, Gupta Rishab K, Cho-Chung Yoon S
Cellular Biochemistry Section, Basic Research Laboratory, National Cancer Institute, Bethesda, MD 20892-1750, USA.
Cancer Res. 2006 Sep 15;66(18):8971-4. doi: 10.1158/0008-5472.CAN-06-1049.
In cancer cells, cyclic AMP-dependent protein kinase (PKA) is secreted into the conditioned medium. This PKA, designated as extracellular protein kinase A (ECPKA), is markedly up-regulated in the sera of patients with cancer. The currently available tumor markers are based on the antigen determination method and lack specificity and sensitivity. Here, we present an ECPKA autoantibody detection method for a universal biomarker that detects cancer of various cell types. We tested sera from 295 patients with cancers of various cell types, 155 normal controls, and 55 patients without cancer. The specificity and sensitivity of this autoantibody enzyme immunoassay method were compared with the conventional antigen determination method by receiver-operating characteristic plots. In the sera, the presence of autoantibody directed against ECPKA was highly correlated with cancer. High anti-ECPKA autoantibody titers (frequency, 90%; mean titer, 3.0) were found in the sera of patients with various cancers, whereas low or negative titers (frequency, 12%; mean titer, 1.0) were found in the control group. The receiver-operating characteristic plot showed that autoantibody enzyme immunoassay exhibited 90% sensitivity and 88% specificity, whereas the enzymatic assay exhibited 83% sensitivity and 80% specificity. These results show that the autoantibody method distinguished between patients with cancer and controls better than the antigen method could. Our results show that autoantibody ECPKA is a universal serum biomarker for cancers of various cell types.
在癌细胞中，环磷酸腺苷依赖性蛋白激酶（PKA）分泌到条件培养基中。这种PKA被称为细胞外蛋白激酶A（ECPKA），在癌症患者的血清中明显上调。目前可用的肿瘤标志物基于抗原测定方法，缺乏特异性和敏感性。在此，我们提出一种用于检测各种细胞类型癌症的通用生物标志物的ECPKA自身抗体检测方法。我们检测了295例各种细胞类型癌症患者、155例正常对照者和55例非癌症患者的血清。通过受试者工作特征曲线将这种自身抗体酶免疫测定方法的特异性和敏感性与传统抗原测定方法进行比较。在血清中，针对ECPKA的自身抗体的存在与癌症高度相关。在各种癌症患者的血清中发现高抗ECPKA自身抗体滴度（频率为90%；平均滴度为3.0），而在对照组中发现低滴度或阴性滴度（频率为12%；平均滴度为1.0）。受试者工作特征曲线显示，自身抗体酶免疫测定的敏感性为90%，特异性为88%，而酶测定的敏感性为83%，特异性为80%。这些结果表明，自身抗体方法在区分癌症患者和对照者方面比抗原方法更好。我们的结果表明，自身抗体ECPKA是各种细胞类型癌症的通用血清生物标志物。
