Investigation of ovarian cancer associated sialylation changes in N-linked glycopeptides by quantitative proteomics

In this study, we investigated the N-linked sialylated glycopeptides in serum samples from healthy and ovarian cancer patients using Lectin-directed Tandem Labeling (LTL) and iTRAQ quantitative proteomics methods. We identified 45 N-linked sialylated glycopeptides containing 46 glycosylation sites. Among those, ten sialylated glycopeptides were significantly up-regulated in ovarian cancer patients’ serum samples. LC-MS/MS analysis of the non-glycosylated peptides from the same samples, western blot data using lectin enriched glycoproteins of various ovarian cancer type samples, and PNGase F (+/？) treatment confirmed the sialylation changes in the ovarian cancer samples.Herein, we demonstrated that several proteins are aberrantly sialylated in N-linked glycopeptides in ovarian cancer and detection of glycopeptides with abnormal sialylation changes may have the potential to serve as biomarkers for ovarian cancer.The American Cancer Society estimates that in 2011, about 21,990 new cases of ovarian cancer will be diagnosed and 15,460 women will die of ovarian cancer in the United States (ovariancancer.org) [1-3]. When ovarian cancer is detected early, the five year survival rate is over 90% [4]. Serum measurement of CA125, the current standard, has an early stage detection rate of only about 28% and when combined with ultrasound still only identifies 48% [5,6]. Development of improved diagnostic tools for early detection of ovarian cancer, including the discovery of new ovarian cancer biomarkers, has the potential to significantly improve the survival rate.It has been shown that in the cancer transformation process, changed expression and post translational modification of proteins occurs, resulting in a change in the protein structure and function. Investigating these modifications specific for cancer may provide vital information and serve as biomarkers for the diseased state. Glycosylation is a common and essential form of post translational modification of proteins.