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

Vivekananda Shetty, Julie Hafner, Punit Shah, Zacharie Nickens, Ramila Philip

Research output: Contribution to journalArticlepeer-review

Abstract

Background: In 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. Results: 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. Conclusion: 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.

Original languageEnglish (US)
Article number10
JournalClinical Proteomics
Volume9
Issue number1
DOIs
StatePublished - 2012
Externally publishedYes

Keywords

  • Lectin
  • Mass spectrometry
  • N-linked glycopeptides
  • Ovarian cancer
  • Quantitative proteomics
  • Sialylation
  • Western blot

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

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