Protein-Specific Differential Glycosylation of Immunoglobulins in Serum of Ovarian Cancer Patients

L. Renee Ruhaak, Kyoungmi Kim, Carol Stroble, Sandra L. Taylor, Qiuting Hong, Suzanne Miyamoto, Carlito B Lebrilla, Gary S Leiserowitz

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Previous studies indicated that glycans in serum may serve as biomarkers for diagnosis of ovarian cancer; however, it was unclear to which proteins these glycans belong. We hypothesize that protein-specific glycosylation profiles of the glycans may be more informative of ovarian cancer and can provide insight into biological mechanisms underlying glycan aberration in serum of diseased individuals. Serum samples from women diagnosed with epithelial ovarian cancer (EOC, n = 84) and matched healthy controls (n = 84) were obtained from the Gynecologic Oncology Group. Immunoglobulin (IgG, IgA, and IgM) concentrations and glycosylation profiles were quantified using multiple reaction monitoring mass spectrometry. Differential and classification analyses were performed to identify aberrant protein-specific glycopeptides using a training set. All findings were validated in an independent test set. Multiple glycopeptides from immunoglubins IgA, IgG, and IgM were found to be differentially expressed in serum of EOC patients compared with controls. The protein-specific glycosylation profiles showed their potential in the diagnosis of EOC. In particular, IgG-specific glycosylation profiles are the most powerful in discriminating between EOC case and controls. Additional studies of protein- and site-specific glycosylation profiles of immunoglobulins and other proteins will allow further elaboration on the characteristics of biological functionality and causality of the differential glycosylation in ovarian cancer and thus ultimately lead to increased sensitivity and specificity of diagnosis.

Original languageEnglish (US)
Pages (from-to)1002-1010
Number of pages9
JournalJournal of Proteome Research
Volume15
Issue number3
DOIs
StatePublished - Mar 4 2016

Fingerprint

Glycosylation
Ovarian Neoplasms
Immunoglobulins
Polysaccharides
Serum
Proteins
Glycopeptides
Immunoglobulin G
Immunoglobulin A
Immunoglobulin M
Oncology
Biomarkers
Aberrations
Causality
Mass spectrometry
Mass Spectrometry
Sensitivity and Specificity
Monitoring

Keywords

  • biomarker
  • immunoglobulin
  • N-glycosylation
  • ovarian cancer
  • serum

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

Protein-Specific Differential Glycosylation of Immunoglobulins in Serum of Ovarian Cancer Patients. / Ruhaak, L. Renee; Kim, Kyoungmi; Stroble, Carol; Taylor, Sandra L.; Hong, Qiuting; Miyamoto, Suzanne; Lebrilla, Carlito B; Leiserowitz, Gary S.

In: Journal of Proteome Research, Vol. 15, No. 3, 04.03.2016, p. 1002-1010.

Research output: Contribution to journalArticle

Ruhaak, L. Renee ; Kim, Kyoungmi ; Stroble, Carol ; Taylor, Sandra L. ; Hong, Qiuting ; Miyamoto, Suzanne ; Lebrilla, Carlito B ; Leiserowitz, Gary S. / Protein-Specific Differential Glycosylation of Immunoglobulins in Serum of Ovarian Cancer Patients. In: Journal of Proteome Research. 2016 ; Vol. 15, No. 3. pp. 1002-1010.
@article{37f187c620574905853310595dc84fea,
title = "Protein-Specific Differential Glycosylation of Immunoglobulins in Serum of Ovarian Cancer Patients",
abstract = "Previous studies indicated that glycans in serum may serve as biomarkers for diagnosis of ovarian cancer; however, it was unclear to which proteins these glycans belong. We hypothesize that protein-specific glycosylation profiles of the glycans may be more informative of ovarian cancer and can provide insight into biological mechanisms underlying glycan aberration in serum of diseased individuals. Serum samples from women diagnosed with epithelial ovarian cancer (EOC, n = 84) and matched healthy controls (n = 84) were obtained from the Gynecologic Oncology Group. Immunoglobulin (IgG, IgA, and IgM) concentrations and glycosylation profiles were quantified using multiple reaction monitoring mass spectrometry. Differential and classification analyses were performed to identify aberrant protein-specific glycopeptides using a training set. All findings were validated in an independent test set. Multiple glycopeptides from immunoglubins IgA, IgG, and IgM were found to be differentially expressed in serum of EOC patients compared with controls. The protein-specific glycosylation profiles showed their potential in the diagnosis of EOC. In particular, IgG-specific glycosylation profiles are the most powerful in discriminating between EOC case and controls. Additional studies of protein- and site-specific glycosylation profiles of immunoglobulins and other proteins will allow further elaboration on the characteristics of biological functionality and causality of the differential glycosylation in ovarian cancer and thus ultimately lead to increased sensitivity and specificity of diagnosis.",
keywords = "biomarker, immunoglobulin, N-glycosylation, ovarian cancer, serum",
author = "Ruhaak, {L. Renee} and Kyoungmi Kim and Carol Stroble and Taylor, {Sandra L.} and Qiuting Hong and Suzanne Miyamoto and Lebrilla, {Carlito B} and Leiserowitz, {Gary S}",
year = "2016",
month = "3",
day = "4",
doi = "10.1021/acs.jproteome.5b01071",
language = "English (US)",
volume = "15",
pages = "1002--1010",
journal = "Journal of Proteome Research",
issn = "1535-3893",
publisher = "American Chemical Society",
number = "3",

}

TY - JOUR

T1 - Protein-Specific Differential Glycosylation of Immunoglobulins in Serum of Ovarian Cancer Patients

AU - Ruhaak, L. Renee

AU - Kim, Kyoungmi

AU - Stroble, Carol

AU - Taylor, Sandra L.

AU - Hong, Qiuting

AU - Miyamoto, Suzanne

AU - Lebrilla, Carlito B

AU - Leiserowitz, Gary S

PY - 2016/3/4

Y1 - 2016/3/4

N2 - Previous studies indicated that glycans in serum may serve as biomarkers for diagnosis of ovarian cancer; however, it was unclear to which proteins these glycans belong. We hypothesize that protein-specific glycosylation profiles of the glycans may be more informative of ovarian cancer and can provide insight into biological mechanisms underlying glycan aberration in serum of diseased individuals. Serum samples from women diagnosed with epithelial ovarian cancer (EOC, n = 84) and matched healthy controls (n = 84) were obtained from the Gynecologic Oncology Group. Immunoglobulin (IgG, IgA, and IgM) concentrations and glycosylation profiles were quantified using multiple reaction monitoring mass spectrometry. Differential and classification analyses were performed to identify aberrant protein-specific glycopeptides using a training set. All findings were validated in an independent test set. Multiple glycopeptides from immunoglubins IgA, IgG, and IgM were found to be differentially expressed in serum of EOC patients compared with controls. The protein-specific glycosylation profiles showed their potential in the diagnosis of EOC. In particular, IgG-specific glycosylation profiles are the most powerful in discriminating between EOC case and controls. Additional studies of protein- and site-specific glycosylation profiles of immunoglobulins and other proteins will allow further elaboration on the characteristics of biological functionality and causality of the differential glycosylation in ovarian cancer and thus ultimately lead to increased sensitivity and specificity of diagnosis.

AB - Previous studies indicated that glycans in serum may serve as biomarkers for diagnosis of ovarian cancer; however, it was unclear to which proteins these glycans belong. We hypothesize that protein-specific glycosylation profiles of the glycans may be more informative of ovarian cancer and can provide insight into biological mechanisms underlying glycan aberration in serum of diseased individuals. Serum samples from women diagnosed with epithelial ovarian cancer (EOC, n = 84) and matched healthy controls (n = 84) were obtained from the Gynecologic Oncology Group. Immunoglobulin (IgG, IgA, and IgM) concentrations and glycosylation profiles were quantified using multiple reaction monitoring mass spectrometry. Differential and classification analyses were performed to identify aberrant protein-specific glycopeptides using a training set. All findings were validated in an independent test set. Multiple glycopeptides from immunoglubins IgA, IgG, and IgM were found to be differentially expressed in serum of EOC patients compared with controls. The protein-specific glycosylation profiles showed their potential in the diagnosis of EOC. In particular, IgG-specific glycosylation profiles are the most powerful in discriminating between EOC case and controls. Additional studies of protein- and site-specific glycosylation profiles of immunoglobulins and other proteins will allow further elaboration on the characteristics of biological functionality and causality of the differential glycosylation in ovarian cancer and thus ultimately lead to increased sensitivity and specificity of diagnosis.

KW - biomarker

KW - immunoglobulin

KW - N-glycosylation

KW - ovarian cancer

KW - serum

UR - http://www.scopus.com/inward/record.url?scp=84960461505&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84960461505&partnerID=8YFLogxK

U2 - 10.1021/acs.jproteome.5b01071

DO - 10.1021/acs.jproteome.5b01071

M3 - Article

C2 - 26813784

AN - SCOPUS:84960461505

VL - 15

SP - 1002

EP - 1010

JO - Journal of Proteome Research

JF - Journal of Proteome Research

SN - 1535-3893

IS - 3

ER -