Identification of O-glycosylated Proteins That Are Aberrantly Excreted in the Urine of Patients with Early Stage Ovarian Cancer

Abstract

Cancer is known to induce or alter the O-glycosylation of selective proteins that may eventually be excreted in the patients’ urine. The present study was performed to identify O-glycosylated proteins that are aberrantly excreted in the urine of patients with early stage ovarian cancer (OCa). These urinary glycoproteins are potential biomarkers for early detection of OCa. In this study, urinary proteins of patients with early stage OCa and age-matched OCa negative women were subjected to two-dimensional gel electrophoresis and detection using a lectin that binds to the O-glycosylated proteins. Our analysis demonstrated significant enhanced expression of clusterin and leucine-rich alpha-2-glycoprotein, but lower levels of kininogen in the urine of the OCa patients compared to the controls. The different altered levels of these urinary glycoproteins were further confirmed using competitive ELISA. Our data are suggestive of the potential use of the aberrantly excreted urinary O-glycosylated proteins as biomarkers for the early detection of OCa, although this requires further validation in a large clinically representative population.

Glycopatterns of Urinary Protein as New Potential Diagnosis Indicators for Diabetic Nephropathy

“…These findings demonstrated that the glycopatterns, especially the glycopatterns modified by Gal/GalNAc, were decreased as occurred in renal insufficiency. Inoue et al reported the global reduction of the binding to lectins in urine samples of DN at macroalbuminuria stage [30]. Our finding further clarified that glycopatterns showed global reduction when occurring in renal insufficiency in stage of overt proteinuria.…”

“…Abnormal glycosylation of certain glycoprotein in urine could be a more sensitive biomarker for disease diagnosis and monitoring. It is reported that aberrantly excreted urinary O -glycosylated proteins (clusterin, leucine-rich alpha-2-glycoprotein, and kininogen) could serve as potential biomarkers for the early detection of early stage ovarian cancer [30]. As a powerful tool, lectin microarray was used to investigate the glycopatterns of protein for decades.…”

OLFM4, KNG1 and Sec24C identified by proteomics and immunohistochemistry as potential markers of early colorectal cancer stages

“…Although its mechanistic role remains unclear in cancer, KNG1 could have antiangiogenic properties and inhibitory actions on proliferation of endothelial cells [44]. Previous studies have shown lower levels of KNG1 in urine or sera of ovarian carcinoma cases and cervical cancer patients respectively [45, 46]. But in these studies the protein detected was KNG1 light chain and not the entire protein.…”

Alterations in the serum proteome profile during the development of ovarian cancer

“…Time-of-flight spectra were generated by averaging 60 laser shots and collected in the positive mode at laser intensity 185 and detector sensitivity 8 with molecular weight optimized from 2,000 to 10,000 Da (15). Mass accuracy was calibrated on the day of measurements before data collection using the All-in-one peptide molecular mass standard (8).…”

“…BPS was also used to perform a 10-fold crossvalidation because the size of the data set was too small for an independent validation set. This process allows the sensitivity and specificity to be predicted for future data and provides an accurate estimate of the predictive accuracy of the selected decision tree (7,13,15).…”