Detection of aggressive prostate cancer associated glycoproteins in urine using glycoproteomics and mass spectrometry

Abstract

Clinical management of prostate cancer remains a significant challenge due to the lack of available tests for guiding treatment decisions. The blood prostate-specific antigen test has facilitated early detection and intervention of prostate cancer. However, blood prostate-specific antigen levels are less effective in distinguishing aggressive from indolent prostate cancers and other benign prostatic diseases. Thus, the development of novel approaches specific for prostate cancer that can differentiate aggressive from indolent disease remains an urgent medical need. In the current study, we evaluated urine specimens from prostate cancer patients using LC-MS/MS, with the aim of identifying effective urinary prostate cancer biomarkers. Glycoproteins from urine samples of prostate cancer patients with different Gleason scores were characterized via solid phase extraction of N-linked glycosite-containing peptides and LC-MS/MS. A total of 2923 unique glycosite-containing peptides were identified. Glycoproteomic comparison on urine and tissues from aggressive and non-aggressive prostate cancers as well as sera from prostate cancer patients revealed that the majority of AG prostate cancer associated glycoproteins were more readily detected in patient’s urine than serum samples. Our data collectively indicate that urine provides a potential source for biomarker testing in patients with AG prostate cancer.

Tissue Proteome Signatures Associated with Five Grades of Prostate Cancer and Benign Prostatic Hyperplasia

“…The lack of good prognostic biomarkers which can distinguish indolent and aggressive PCa has contributed to a significant overtreatment of patients. Efforts have been conducted in order to discover novel candidate biomarker for PCa aggressiveness …”

Molecular correlates in urine for the obesity and prostatic inflammation of BPH/LUTS patients

“…Anatomic continuity of prostate with urethra facilitates the preferential drainage of overexpressed chemokines in prostate via shedding and budding of micro and multivesicular bodies from plasma membrane . Urine is therefore biased towards detection of proteins that are overexpressed in prostate tissue such as CCL2 and PSA, which are then secreted into detectable levels urine.…”

“…Chemokines primarily produced in stroma (CCL2) 16 Anatomic continuity of prostate with urethra facilitates the preferential drainage of overexpressed chemokines in prostate via shedding and budding of micro and multivesicular bodies from plasma membrane. 29 Urine is therefore biased towards detection of proteins that are overexpressed in prostate tissue such as CCL2 30 and PSA, 31 which are then secreted into detectable levels urine. In fact, 100 fold higher levels of PSA 31 in urine over serum are commensurate with direct secretion from prostate into urine instead of increased excretion of a 26 kDa protein 32 from a properly functioning kidney of BPH patients.…”

Human Periprostatic Adipose Tissue: Secretome from Patients With Prostate Cancer or Benign Prostate Hyperplasia

“…Vitamin D-binding protein (GC), zinc-alpha-2-glycoprotein (AZGP1), elongation factor 1-alpha 1 (EEF1A1) and hemopexin (HPX) were detected in CM-T3 by us and were found increased in metastatic versus progressing cancer by the same authors. Glycoproteins associated to cancer could also be detected in CM-T3 secretome like periostin (POSTN), versican core protein (VCAN), fibrillin-1 (FBN1) and laminin subunit beta-2 (LAMB2) which was also found in urine, while zinc-alpha-2-glycoprotein (AZGP1) was found in urine and serum of aggressive PCa in a glycoproteomic work (91). Relative protein quantification.…”