Download Carbonic Anhydrase I as a Novel Plasma Biomarker for Prostate

Carbonic Anhydrase I as a Novel Plasma Biomarker for Prostate Cancer
Introduction and Objectives: Prostate-specific antigen (PSA) levels between 4 to 10 ng/ml is considered
diagnostic gray zone for finding prostate cancer, in which a biopsy would reveal no evidence of cancer in
75%. In order to discover a new biomarker with higher specificity for prostate cancer, we searched
plasma proteins by our original proteomic technique.
Materials and Methods: Plasma proteins from 27 localized prostate cancer patients and 23 healthy
controls were treated by hollow-fiber-membrane-based low-molecular-weight protein enrichment device
and digested by trypsin, and resulting peptides were analyzed by label-free quantitative shotgun
proteome platform 2DICAL (2-Dimensional Image Converted Analysis of Liquid chromatography mass
spectrometry). An identified biomarker candidate was subjected to validation using the ELISA, and was
analyzed by reverse transcription-PCR, western blot and immunofluorescence staining to elucidate the
characterization.
Results: Of 54,380 identified MS peaks, 179 peaks were significantly different between prostate cancer
patients and healthy controls by 2DICAL. Among the 179 peaks, ten peaks matched to carbonic
anhydrase I (CAI) gene product by tandem mass analysis. The plasma levels of the CAI were statistically
significant between 54 prostate cancer patients and 81 health controls (P = 0.014, Mann-Whitney U test).
In PSA gray zone group, the discrimination rate of prostate cancer patients increased counting on CAI
plasma concentration. The cellular expressions of CAI gene and gene product were determined in
prostate cancer cells. CAI was localized at cytoplasm by immunofluorescence staining.
Conclusion: CAI can be a plasma biomarker of prostate cancer in conjunction with current standard
diagnostic procedure.