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 journalArticle

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

Fingerprint

Glycopeptides
Proteomics
Ovarian Neoplasms
Lectins
Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase
Glycosylation
Biomarkers
Labeling
Glycoproteins
Screening
Peptides
Serum
Early Diagnosis
Western Blotting
Proteins
Sensitivity and Specificity

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Clinical Biochemistry

Cite this

Investigation of ovarian cancer associated sialylation changes in N-linked glycopeptides by quantitative proteomics. / Shetty, Vivekananda; Hafner, Julie; Shah, Punit; Nickens, Zacharie; Philip, Ramila.

In: Clinical Proteomics, Vol. 9, No. 1, 10, 2012.

Research output: Contribution to journalArticle

Shetty, Vivekananda ; Hafner, Julie ; Shah, Punit ; Nickens, Zacharie ; Philip, Ramila. / Investigation of ovarian cancer associated sialylation changes in N-linked glycopeptides by quantitative proteomics. In: Clinical Proteomics. 2012 ; Vol. 9, No. 1.
@article{389306ff7f614de3bad7e237e5f979f6,
title = "Investigation of ovarian cancer associated sialylation changes in N-linked glycopeptides by quantitative proteomics",
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.",
keywords = "Lectin, Mass spectrometry, N-linked glycopeptides, Ovarian cancer, Quantitative proteomics, Sialylation, Western blot",
author = "Vivekananda Shetty and Julie Hafner and Punit Shah and Zacharie Nickens and Ramila Philip",
year = "2012",
doi = "10.1186/1559-0275-9-10",
language = "English (US)",
volume = "9",
journal = "Clinical Proteomics",
issn = "1542-6416",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Investigation of ovarian cancer associated sialylation changes in N-linked glycopeptides by quantitative proteomics

AU - Shetty, Vivekananda

AU - Hafner, Julie

AU - Shah, Punit

AU - Nickens, Zacharie

AU - Philip, Ramila

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

KW - Lectin

KW - Mass spectrometry

KW - N-linked glycopeptides

KW - Ovarian cancer

KW - Quantitative proteomics

KW - Sialylation

KW - Western blot

UR - http://www.scopus.com/inward/record.url?scp=84877023639&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84877023639&partnerID=8YFLogxK

U2 - 10.1186/1559-0275-9-10

DO - 10.1186/1559-0275-9-10

M3 - Article

C2 - 22856521

AN - SCOPUS:84877023639

VL - 9

JO - Clinical Proteomics

JF - Clinical Proteomics

SN - 1542-6416

IS - 1

M1 - 10

ER -