Integrative Analysis of N-Linked Human Glycoproteomic Data Sets Reveals PTPRF Ectodomain as a Novel Plasma Biomarker Candidate for Prostate Cancer

In an attempt to identify prostate cancer biomarkers
with greater diagnostic and prognostic capabilities, we have developed
an integrative proteomic discovery workflow focused on N-linked glycoproteins
that refines the target selection process. In this work, hydrazide-based
chemistry was used to identify N-linked glycopeptides from 22Rv1 prostate
cancer cells cultured in vitro, which were compared with glycopeptides
identified from explanted 22Rv1 murine tumor xenografts. One hundred
and four human glycoproteins were identified in the former analysis
and 75 in the latter, with 40 proteins overlapping between data sets.
Of the 40 overlapping proteins, 80% have multiple literature references
to the neoplastic process and ∼40% to prostatic neoplasms. These include a number of well-known prostate cancer-associated
biomarkers, such as prostate-specific membrane antigen (PSMA). By
integrating gene expression data and available literature, we identified
members of the overlap data set that deserve consideration as potential
prostate cancer biomarkers. Specifically, the identification of the
extracellular domain of protein tyrosine phosphatase receptor type
F (PTPRF) was of particular interest due to the direct involvement
of PTPRF in the control of β-catenin signaling, as well as dramatically
elevated gene expression levels in the prostate compared to other
tissues. In this investigation, we demonstrate that the PTPRF E-subunit
is more abundant in human prostate tumor tissue compared to normal
control and also detectable in murine plasma by immunoblot and ELISA.
Specifically, PTPRF distinguishes between animals xenografted with
the 22Rv1 cells and control animals as early as 14 days after implantation.
This result suggests that the ectodomain of PTPRF has the potential
to function as a novel plasma or tissue-based biomarker for prostate
cancer. The workflow described adds to the literature of potential
biomarker candidates for prostate cancer and demonstrates a pathway
to developing new diagnostic assays.