Isomer-specific chromatographic profiling yields highly sensitive and specific potential N-glycan biomarkers for epithelial ovarian cancer

Serenus Hua, Cynthia C. Williams, Lauren M. Dimapasoc, Grace S. Ro, Sureyya Ozcan, Suzanne Miyamoto, Carlito B Lebrilla, Hyun Joo An, Gary S Leiserowitz

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Aberrant glycosylation has been observed for decades in essentially all types of cancer, and is now well established as an indicator of carcinogenesis. Mining the glycome for biomarkers, however, requires analytical methods that can rapidly separate, identify, and quantify isomeric glycans. We have developed a rapid-throughput method for chromatographic glycan profiling using microfluidic chip-based nanoflow liquid chromatography (nano-LC)/mass spectrometry. To demonstrate the utility of this method, we analyzed and compared serum samples from epithelial ovarian cancer cases (n=46) and healthy control individuals (n=48). Over 250 N-linked glycan compound peaks with over 100 distinct N-linked glycan compositions were identified. Statistical testing identified 26 potential glycan biomarkers based on both compositional and structure-specific analyses. Using these results, an optimized model was created incorporating the combined abundances of seven potential glycan biomarkers. The receiver operating characteristic (ROC) curve of this optimized model had an area under the curve (AUC) of 0.96, indicating robust discrimination between cancer cases and healthy controls. Rapid-throughput chromatographic glycan profiling was found to be an effective platform for structure-specific biomarker discovery.

Original languageEnglish (US)
Pages (from-to)58-67
Number of pages10
JournalJournal of Chromatography A
Volume1279
DOIs
StatePublished - Mar 1 2013

Fingerprint

Biomarkers
Isomers
Polysaccharides
Throughput
Glycosylation
Microfluidics
Liquid chromatography
Ovarian epithelial cancer
ROC Curve
Liquid Chromatography
Area Under Curve
Mass spectrometry
Mass Spectrometry
Neoplasms
Carcinogenesis
Testing
Serum
Chemical analysis

Keywords

  • Cancer biomarker
  • Chip nano-LC/MS
  • Glycan isomer separation
  • Rapid-throughput
  • Serum glycan
  • Structure-specific profiling

ASJC Scopus subject areas

  • Analytical Chemistry
  • Organic Chemistry
  • Biochemistry

Cite this

Isomer-specific chromatographic profiling yields highly sensitive and specific potential N-glycan biomarkers for epithelial ovarian cancer. / Hua, Serenus; Williams, Cynthia C.; Dimapasoc, Lauren M.; Ro, Grace S.; Ozcan, Sureyya; Miyamoto, Suzanne; Lebrilla, Carlito B; An, Hyun Joo; Leiserowitz, Gary S.

In: Journal of Chromatography A, Vol. 1279, 01.03.2013, p. 58-67.

Research output: Contribution to journalArticle

Hua, Serenus ; Williams, Cynthia C. ; Dimapasoc, Lauren M. ; Ro, Grace S. ; Ozcan, Sureyya ; Miyamoto, Suzanne ; Lebrilla, Carlito B ; An, Hyun Joo ; Leiserowitz, Gary S. / Isomer-specific chromatographic profiling yields highly sensitive and specific potential N-glycan biomarkers for epithelial ovarian cancer. In: Journal of Chromatography A. 2013 ; Vol. 1279. pp. 58-67.
@article{234ca2da9aeb476caa85125944cd0993,
title = "Isomer-specific chromatographic profiling yields highly sensitive and specific potential N-glycan biomarkers for epithelial ovarian cancer",
abstract = "Aberrant glycosylation has been observed for decades in essentially all types of cancer, and is now well established as an indicator of carcinogenesis. Mining the glycome for biomarkers, however, requires analytical methods that can rapidly separate, identify, and quantify isomeric glycans. We have developed a rapid-throughput method for chromatographic glycan profiling using microfluidic chip-based nanoflow liquid chromatography (nano-LC)/mass spectrometry. To demonstrate the utility of this method, we analyzed and compared serum samples from epithelial ovarian cancer cases (n=46) and healthy control individuals (n=48). Over 250 N-linked glycan compound peaks with over 100 distinct N-linked glycan compositions were identified. Statistical testing identified 26 potential glycan biomarkers based on both compositional and structure-specific analyses. Using these results, an optimized model was created incorporating the combined abundances of seven potential glycan biomarkers. The receiver operating characteristic (ROC) curve of this optimized model had an area under the curve (AUC) of 0.96, indicating robust discrimination between cancer cases and healthy controls. Rapid-throughput chromatographic glycan profiling was found to be an effective platform for structure-specific biomarker discovery.",
keywords = "Cancer biomarker, Chip nano-LC/MS, Glycan isomer separation, Rapid-throughput, Serum glycan, Structure-specific profiling",
author = "Serenus Hua and Williams, {Cynthia C.} and Dimapasoc, {Lauren M.} and Ro, {Grace S.} and Sureyya Ozcan and Suzanne Miyamoto and Lebrilla, {Carlito B} and An, {Hyun Joo} and Leiserowitz, {Gary S}",
year = "2013",
month = "3",
day = "1",
doi = "10.1016/j.chroma.2012.12.079",
language = "English (US)",
volume = "1279",
pages = "58--67",
journal = "Journal of Chromatography",
issn = "0021-9673",
publisher = "Elsevier",

}

TY - JOUR

T1 - Isomer-specific chromatographic profiling yields highly sensitive and specific potential N-glycan biomarkers for epithelial ovarian cancer

AU - Hua, Serenus

AU - Williams, Cynthia C.

AU - Dimapasoc, Lauren M.

AU - Ro, Grace S.

AU - Ozcan, Sureyya

AU - Miyamoto, Suzanne

AU - Lebrilla, Carlito B

AU - An, Hyun Joo

AU - Leiserowitz, Gary S

PY - 2013/3/1

Y1 - 2013/3/1

N2 - Aberrant glycosylation has been observed for decades in essentially all types of cancer, and is now well established as an indicator of carcinogenesis. Mining the glycome for biomarkers, however, requires analytical methods that can rapidly separate, identify, and quantify isomeric glycans. We have developed a rapid-throughput method for chromatographic glycan profiling using microfluidic chip-based nanoflow liquid chromatography (nano-LC)/mass spectrometry. To demonstrate the utility of this method, we analyzed and compared serum samples from epithelial ovarian cancer cases (n=46) and healthy control individuals (n=48). Over 250 N-linked glycan compound peaks with over 100 distinct N-linked glycan compositions were identified. Statistical testing identified 26 potential glycan biomarkers based on both compositional and structure-specific analyses. Using these results, an optimized model was created incorporating the combined abundances of seven potential glycan biomarkers. The receiver operating characteristic (ROC) curve of this optimized model had an area under the curve (AUC) of 0.96, indicating robust discrimination between cancer cases and healthy controls. Rapid-throughput chromatographic glycan profiling was found to be an effective platform for structure-specific biomarker discovery.

AB - Aberrant glycosylation has been observed for decades in essentially all types of cancer, and is now well established as an indicator of carcinogenesis. Mining the glycome for biomarkers, however, requires analytical methods that can rapidly separate, identify, and quantify isomeric glycans. We have developed a rapid-throughput method for chromatographic glycan profiling using microfluidic chip-based nanoflow liquid chromatography (nano-LC)/mass spectrometry. To demonstrate the utility of this method, we analyzed and compared serum samples from epithelial ovarian cancer cases (n=46) and healthy control individuals (n=48). Over 250 N-linked glycan compound peaks with over 100 distinct N-linked glycan compositions were identified. Statistical testing identified 26 potential glycan biomarkers based on both compositional and structure-specific analyses. Using these results, an optimized model was created incorporating the combined abundances of seven potential glycan biomarkers. The receiver operating characteristic (ROC) curve of this optimized model had an area under the curve (AUC) of 0.96, indicating robust discrimination between cancer cases and healthy controls. Rapid-throughput chromatographic glycan profiling was found to be an effective platform for structure-specific biomarker discovery.

KW - Cancer biomarker

KW - Chip nano-LC/MS

KW - Glycan isomer separation

KW - Rapid-throughput

KW - Serum glycan

KW - Structure-specific profiling

UR - http://www.scopus.com/inward/record.url?scp=84873283213&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84873283213&partnerID=8YFLogxK

U2 - 10.1016/j.chroma.2012.12.079

DO - 10.1016/j.chroma.2012.12.079

M3 - Article

C2 - 23380366

AN - SCOPUS:84873283213

VL - 1279

SP - 58

EP - 67

JO - Journal of Chromatography

JF - Journal of Chromatography

SN - 0021-9673

ER -