Abstract
BackgroundIn approximately 80% of patients, ovarian cancer is diagnosed when the patient is already in the advanced stages of the disease. CA125 is currently used as the marker for ovarian cancer; however, it lacks specificity and sensitivity for detecting early stage disease. There is a critical unmet need for sensitive and specific routine screening tests for early diagnosis that can reduce ovarian cancer lethality by reliably detecting the disease at its earliest and treatable stages.ResultsIn 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.ConclusionHerein, 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.
Highlights
In approximately 80% of patients, ovarian cancer is diagnosed when the patient is already in the advanced stages of the disease
Equal amounts (5 mg each) of protein from normal and cancer serum samples were digested by trypsin and glycopeptides containing sialic acid were enriched by using Sambucus nigra lectin (SNA) lectin
Identification of low abundant serum proteins including PON 1 (25 μg/mL) [31], Ficolin-3 (32.4 μg/mL) [32], and Kallikrein (2.9 μg/mL) [33] in our analysis demonstrate the high sensitivity of the Lectin-directed Tandem Labeling (LTL) method
Summary
In approximately 80% of patients, ovarian cancer is diagnosed when the patient is already in the advanced stages of the disease. 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. Increased activity of sialyltransferase is shown to be accompanied by an increase in the level of enzymes, such as ST6Gal-1, which is responsible for linking sialic acid to galactose in colorectal, ovarian and breast cancers [10,12,13,14]. ST6Gal-1 has been implicated in cell-cell interaction, enhanced motility and increased invasiveness of tumor cells [10]
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