Evaluation of glycomic profiling as a diagnostic biomarker for epithelial ovarian cancer

Kyoungmi Kim, L. Renee Ruhaak, Uyen Thao Nguyen, Sandra L. Taylor, Lauren Dimapasoc, Cynthia Williams, Carol Stroble, Sureyya Ozcan, Suzanne Miyamoto, Carlito B Lebrilla, Gary S Leiserowitz

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Background: Prior studies suggested that glycans were differentially expressed in patients with ovarian cancer and controls. We hypothesized that glycan-based biomarkers might serve as a diagnostic test for ovarian cancer and evaluated the ability of glycans to distinguish ovarian cancer cases from matched controls. Methods: Serum samples were obtained from the tissue-banking repository of the Gynecologic Oncology Group, and included healthy female controls (n = 100), women diagnosed with low malignant potential (LMP) tumors (n = 52), and epithelial ovarian cancers (EOC) cases (n = 147). Cases and controls were matched on age at enrollment within ±5 years. Serum samples were analyzed by glycomics analysis to detect abundance differences in glycan expression levels. A two-stage procedure was carried out for biomarker discovery and validation. Candidate classifiers of glycans that separated cases from controls were developed using a training set in the discovery phase and the classification performance of the candidate classifiers was assessed using independent test samples that were not used in discovery. Results: The patterns of glycans showed discriminatory power for distinguishing EOC and LMP cases from controls. Candidate glycan-based biomarkers developed on a training set (sensitivity, 86% and specificity, 95.8% for distinguishing EOC from controls through leave-one-out cross-validation) confirmed their potential use as a detection test using an independent test set (sensitivity, 70% and specificity, 86.5%). Conclusion: Formal investigations of glycan biomarkers that distinguish cases and controls show great promise for an ovarian cancer diagnostic test. Further validation of a glycan-based test for detection of ovarian cancer is warranted. Impact: An emerging diagnostic test based on the knowledge gained from understanding the glycobiology should lead to an assay that improves sensitivity and specificity and allows for early detection of ovarian cancer.

Original languageEnglish (US)
Pages (from-to)611-621
Number of pages11
JournalCancer Epidemiology Biomarkers and Prevention
Volume23
Issue number4
DOIs
StatePublished - 2014

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Glycomics
Polysaccharides
Biomarkers
Ovarian Neoplasms
Sensitivity and Specificity
Routine Diagnostic Tests
Tissue Banks
Ovarian epithelial cancer
Serum
Early Detection of Cancer

ASJC Scopus subject areas

  • Epidemiology
  • Oncology
  • Medicine(all)

Cite this

Evaluation of glycomic profiling as a diagnostic biomarker for epithelial ovarian cancer. / Kim, Kyoungmi; Ruhaak, L. Renee; Nguyen, Uyen Thao; Taylor, Sandra L.; Dimapasoc, Lauren; Williams, Cynthia; Stroble, Carol; Ozcan, Sureyya; Miyamoto, Suzanne; Lebrilla, Carlito B; Leiserowitz, Gary S.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 23, No. 4, 2014, p. 611-621.

Research output: Contribution to journalArticle

Kim, K, Ruhaak, LR, Nguyen, UT, Taylor, SL, Dimapasoc, L, Williams, C, Stroble, C, Ozcan, S, Miyamoto, S, Lebrilla, CB & Leiserowitz, GS 2014, 'Evaluation of glycomic profiling as a diagnostic biomarker for epithelial ovarian cancer', Cancer Epidemiology Biomarkers and Prevention, vol. 23, no. 4, pp. 611-621. https://doi.org/10.1158/1055-9965.EPI-13-1073
Kim, Kyoungmi ; Ruhaak, L. Renee ; Nguyen, Uyen Thao ; Taylor, Sandra L. ; Dimapasoc, Lauren ; Williams, Cynthia ; Stroble, Carol ; Ozcan, Sureyya ; Miyamoto, Suzanne ; Lebrilla, Carlito B ; Leiserowitz, Gary S. / Evaluation of glycomic profiling as a diagnostic biomarker for epithelial ovarian cancer. In: Cancer Epidemiology Biomarkers and Prevention. 2014 ; Vol. 23, No. 4. pp. 611-621.
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abstract = "Background: Prior studies suggested that glycans were differentially expressed in patients with ovarian cancer and controls. We hypothesized that glycan-based biomarkers might serve as a diagnostic test for ovarian cancer and evaluated the ability of glycans to distinguish ovarian cancer cases from matched controls. Methods: Serum samples were obtained from the tissue-banking repository of the Gynecologic Oncology Group, and included healthy female controls (n = 100), women diagnosed with low malignant potential (LMP) tumors (n = 52), and epithelial ovarian cancers (EOC) cases (n = 147). Cases and controls were matched on age at enrollment within ±5 years. Serum samples were analyzed by glycomics analysis to detect abundance differences in glycan expression levels. A two-stage procedure was carried out for biomarker discovery and validation. Candidate classifiers of glycans that separated cases from controls were developed using a training set in the discovery phase and the classification performance of the candidate classifiers was assessed using independent test samples that were not used in discovery. Results: The patterns of glycans showed discriminatory power for distinguishing EOC and LMP cases from controls. Candidate glycan-based biomarkers developed on a training set (sensitivity, 86{\%} and specificity, 95.8{\%} for distinguishing EOC from controls through leave-one-out cross-validation) confirmed their potential use as a detection test using an independent test set (sensitivity, 70{\%} and specificity, 86.5{\%}). Conclusion: Formal investigations of glycan biomarkers that distinguish cases and controls show great promise for an ovarian cancer diagnostic test. Further validation of a glycan-based test for detection of ovarian cancer is warranted. Impact: An emerging diagnostic test based on the knowledge gained from understanding the glycobiology should lead to an assay that improves sensitivity and specificity and allows for early detection of ovarian cancer.",
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AU - Ruhaak, L. Renee

AU - Nguyen, Uyen Thao

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AU - Dimapasoc, Lauren

AU - Williams, Cynthia

AU - Stroble, Carol

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AU - Lebrilla, Carlito B

AU - Leiserowitz, Gary S

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N2 - Background: Prior studies suggested that glycans were differentially expressed in patients with ovarian cancer and controls. We hypothesized that glycan-based biomarkers might serve as a diagnostic test for ovarian cancer and evaluated the ability of glycans to distinguish ovarian cancer cases from matched controls. Methods: Serum samples were obtained from the tissue-banking repository of the Gynecologic Oncology Group, and included healthy female controls (n = 100), women diagnosed with low malignant potential (LMP) tumors (n = 52), and epithelial ovarian cancers (EOC) cases (n = 147). Cases and controls were matched on age at enrollment within ±5 years. Serum samples were analyzed by glycomics analysis to detect abundance differences in glycan expression levels. A two-stage procedure was carried out for biomarker discovery and validation. Candidate classifiers of glycans that separated cases from controls were developed using a training set in the discovery phase and the classification performance of the candidate classifiers was assessed using independent test samples that were not used in discovery. Results: The patterns of glycans showed discriminatory power for distinguishing EOC and LMP cases from controls. Candidate glycan-based biomarkers developed on a training set (sensitivity, 86% and specificity, 95.8% for distinguishing EOC from controls through leave-one-out cross-validation) confirmed their potential use as a detection test using an independent test set (sensitivity, 70% and specificity, 86.5%). Conclusion: Formal investigations of glycan biomarkers that distinguish cases and controls show great promise for an ovarian cancer diagnostic test. Further validation of a glycan-based test for detection of ovarian cancer is warranted. Impact: An emerging diagnostic test based on the knowledge gained from understanding the glycobiology should lead to an assay that improves sensitivity and specificity and allows for early detection of ovarian cancer.

AB - Background: Prior studies suggested that glycans were differentially expressed in patients with ovarian cancer and controls. We hypothesized that glycan-based biomarkers might serve as a diagnostic test for ovarian cancer and evaluated the ability of glycans to distinguish ovarian cancer cases from matched controls. Methods: Serum samples were obtained from the tissue-banking repository of the Gynecologic Oncology Group, and included healthy female controls (n = 100), women diagnosed with low malignant potential (LMP) tumors (n = 52), and epithelial ovarian cancers (EOC) cases (n = 147). Cases and controls were matched on age at enrollment within ±5 years. Serum samples were analyzed by glycomics analysis to detect abundance differences in glycan expression levels. A two-stage procedure was carried out for biomarker discovery and validation. Candidate classifiers of glycans that separated cases from controls were developed using a training set in the discovery phase and the classification performance of the candidate classifiers was assessed using independent test samples that were not used in discovery. Results: The patterns of glycans showed discriminatory power for distinguishing EOC and LMP cases from controls. Candidate glycan-based biomarkers developed on a training set (sensitivity, 86% and specificity, 95.8% for distinguishing EOC from controls through leave-one-out cross-validation) confirmed their potential use as a detection test using an independent test set (sensitivity, 70% and specificity, 86.5%). Conclusion: Formal investigations of glycan biomarkers that distinguish cases and controls show great promise for an ovarian cancer diagnostic test. Further validation of a glycan-based test for detection of ovarian cancer is warranted. Impact: An emerging diagnostic test based on the knowledge gained from understanding the glycobiology should lead to an assay that improves sensitivity and specificity and allows for early detection of ovarian cancer.

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