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Extracellular Activity of Cyclic AMP–Dependent Protein Kinase as a Biomarker for Human Cancer Detection: Distribution Characteristics in a Normal Population and Cancer Patients

¹ Division of Clinical Pharmacology, Department of Pharmacology and Toxicology, and ² Cancer Pharmacology Laboratory, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama; ³ Institute for Nutritional Sciences, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, and ⁴ Fudan University, Shanghai, P.R. China; ⁵ Haimen Municipal Cancer Institute, Haimen Municipal Center for Disease Control and Prevention, Haimen, Jiangsu, P.R. China; ⁶ Third People's Hospital, Nantong, P.R. China; ⁷ Cancer Hospital (Institute), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, P.R. China; ⁸ Heping Hospital, Changzhi Medical College, Shanxi, P.R. China; and ⁹ Liaoning University, Shenyang, P.R. China

Requests for reprints: Ruiwen Zhang, Division of Clinical Pharmacology, Department of Pharmacology and Toxicology, University of Alabama at Birmingham, VH 113, Box 600, 1670 University Boulevard, Birmingham, AL 35294. Phone: 205-934-8558; Fax: 205-975-9330; E-mail: ruiwen.zhang{at}ccc.uab.edu

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. (Cancer Epidemiol Biomarkers Prev 2007;16(4):789–95)

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