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 language | English (US) |
|---|---|
| Pages (from-to) | 58-67 |
| Number of pages | 10 |
| Journal | Journal of Chromatography A |
| Volume | 1279 |
| DOIs | |
| State | Published - Mar 1 2013 |
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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 journal › Article
}
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 -