Early detection of
prostate cancer is problematic due to the lack of a marker that has high diagnostic
sensitivity and specificity. The
prostate specific antigen (PSA) test, in combination with
digital rectal examination, is the
gold standard for
prostate cancer diagnosis. However, this modality
suffers from low specificity. Therefore, specific markers for clinically relevant
prostate cancer are needed. Our objective was to proteomically characterize the conditioned media from three human
prostate cancer cell lines of differing origin [
PC3 (
bone metastasis),
LNCaP (
lymph node metastasis), and 22Rv1 (localized to
prostate)] to identify
secreted proteins that could serve as novel
prostate cancer biomarkers. Each
cell line was cultured in triplicate, followed by a bottom-up analysis of the
peptides by
two-dimensional chromatography and tandem
mass spectrometry. Approximately, 12% (329) of the proteins identified were classified as
extracellular and 18% (504) as
membrane-bound among which were known
prostate cancer biomarkers such as PSA and
KLK2. To select the most promising candidates for further investigation, tissue specificity, biological function, disease association based on literature searches, and comparison of protein overlap with the
proteome of seminal plasma and serum were examined. On the basis of this, four novel candidates,
follistatin,
chemokine (C-X-C motif) ligand 16,
pentraxin 3 and spondin 2, were validated in the serum of patients with and without
prostate cancer. The proteins presented in this study represent a comprehensive sampling of the
secreted and shed proteins expressed by
prostate cancer cells, which may be useful as diagnostic,
prognostic or predictive
serological markers for
prostate cancer.
