Targeted detection of prostate cancer proteins in serum using heavy-isotope-labeled-peptide standards and MALDI-TOF/TOF

Proteins released from cancer tissues to patient sera can potentially be used to achieve sensitive, specific, and early detection of cancer by means of blood tests. In this study, we used a platform that combines glycopeptide capture, heavy-isotope-labeled-peptide standards, and liquid chromatography coupled to tandem mass spectrometry to determine which glycoproteins from prostate cancer can be detected in sera from patients with early-stage prostate cancer. The detection limit for prostate-specific antigen in serum was 3.44 ng/mL; thus, direct identification of low abundance, cancer-specific proteins was achieved using our platform. We showed that prostatic acid phosphatase and membrane metallo-endopeptidase that were detected in sera were preferentially expressed in prostate cancer tissues. Levels of these two proteins were elevated in biopsy-positive patients but not biopsy-negative groups. Therefore, these two proteins are candidate biomarkers for analysis of patient samples with levels of prostate-specific antigen in the diagnostic gray zone.