Wang Hui, Li Mao, Lin Wenyao, Wang Wenquan, Zhang Zhuo, Rayburn Elizabeth R, Lu Jian, Chen Deng, Yue Xinsen, Shen Fuming, Jiang Feng, He Jie, Wei Wu, Zeng Xiaofei, Zhang Ruiwen
Division of Clinical Pharmacology, Department of Pharmacology and Toxicology, University of Alabama at Birmingham, VH 113, Box 600, 1670 University Boulevard, Birmingham, AL 35294, USA.
Cancer Epidemiol Biomarkers Prev. 2007 Apr;16(4):789-95. doi: 10.1158/1055-9965.EPI-06-0367.
The overexpression of cyclic AMP (cAMP)-dependent protein kinase (PKA) has been reported in patients with cancer, and PKA inhibitors have been tested in clinical trials as a novel cancer therapy. The present study was designed to characterize the population distribution of extracellular activity of cAMP-dependent protein kinase (ECPKA) and its potential value as a biomarker for cancer detection and monitoring of cancer therapy. The population distribution of ECPKA activity was determined in serum samples from a Chinese population consisting of a total of 603 subjects (374 normal healthy volunteers and 229 cancer patients). The serum ECPKA was determined by a validated sensitive radioassay, and its diagnostic values (including positive and negative predictive values) were analyzed. The majority of normal subjects (>70%) have undetectable or very low levels of serum ECPKA. In contrast, the majority of cancer patients (>85%) have high levels of ECPKA. The mean ECPKA activity in the sera of cancer patients was 10.98 units/mL, 5-fold higher than that of the healthy controls (2.15 units/mL; P < 0.001). In both normal subjects and cancer patients, gender and age had no significant influence on the serum ECPKA. Among factors considered, logistic analysis revealed that the disease (cancer) is the only factor contributing to the elevation of ECPKA activity in cancer patients. In conclusion, ECPKA may function as a cancer marker for various human cancers and can be used in cancer detection and for monitoring response to therapy with other screening or diagnostic techniques.
据报道，癌症患者中存在环磷酸腺苷（cAMP）依赖性蛋白激酶（PKA）的过表达，并且PKA抑制剂已在临床试验中作为一种新型癌症治疗方法进行了测试。本研究旨在表征cAMP依赖性蛋白激酶细胞外活性（ECPKA）的人群分布及其作为癌症检测和癌症治疗监测生物标志物的潜在价值。在总共603名受试者（374名正常健康志愿者和229名癌症患者）组成的中国人群的血清样本中测定了ECPKA活性的人群分布。通过经过验证的灵敏放射测定法测定血清ECPKA，并分析其诊断价值（包括阳性和阴性预测值）。大多数正常受试者（>70%）的血清ECPKA水平无法检测到或非常低。相比之下，大多数癌症患者（>85%）的ECPKA水平较高。癌症患者血清中的平均ECPKA活性为10.98单位/毫升，比健康对照组（2.15单位/毫升；P<0.001）高5倍。在正常受试者和癌症患者中，性别和年龄对血清ECPKA均无显著影响。在考虑的因素中，逻辑分析显示疾病（癌症）是导致癌症患者ECPKA活性升高的唯一因素。总之，ECPKA可能作为各种人类癌症的癌症标志物，可用于癌症检测以及与其他筛查或诊断技术一起监测治疗反应。
