Diagnostic Potential of Serum Proteomic Patterns in Prostate Cancer

Abstract

The serum prostate specific antigen test has been widely used in the last decade as an effective screening tool for prostate cancer (CaP). However, the high false-positive rate of the serum prostate specific antigen test necessitates the development of more accurate diagnostic and prognostic biomarkers for CaP. Promising diagnostic potential of serum protein patterns detected by surface enhanced laser desorption/ionization time of flight mass spectrometry for CaP has recently been reported. Independent evaluation of this new technology is warranted to realize its translational utility. We determined whether serum protein profiling by surface enhanced laser desorption/ionization time of flight mass spectrometry and a decision tree algorithm classification system could accurately discriminate between patients with CaP and unaffected individuals. Proteomic spectra of crude serum were generated using the Ciphergen ProteinChip System and pattern detection was performed using Biomarker Patterns Software (Ciphergen Biosystems, Inc., Fremont, California). A total of 106 patients with CaP and 56 controls were randomly allocated to a training set and a test set. The training set, which consisted of 44 patients with cancer and 30 controls, was used to build a decision tree algorithm. The test set, which consisted of 62 patients with cancer and 26 controls, was used in blinded fashion to validate the decision tree. Accuracy of classification using the test set was 67% and 42% for the weak cation exchange array and the copper metal affinity capture array, respectively. Combined spectral data from the weak cation exchange and copper metal affinity capture arrays generated an algorithm that achieved 85% sensitivity and 85% specificity for the detection of CaP. These preliminary findings support recent observations that complex protein profiles have promising potential for the early detection of CaP and warrant future studies with streamlined technology. Furthermore, the combined effect of using 2 array types can greatly enhance the ability of protein profile patterns, suggesting the potential usefulness of alternative approaches to evaluate this new emerging technology.