Glycosylation variants of mucins and CEACAMs as candidate biomarkers for the diagnosis of pancreatic cystic neoplasms

Brian B. Haab, Andrew Porter, Tingting Yue, Lin Li, James Scheiman, Michelle A. Anderson, Dawn Barnes, C. Schmidt, Ziding Feng, Diane M. Simeone

Research output: Contribution to journalArticle

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Abstract

BACKGROUND AND AIMS: Cystic lesions of the pancreas are increasingly being recognized due to the widespread use of high resolution abdominal imaging. Since certain cyst types are precursors to invasive cancer, this situation presents an opportunity to intervene prior to malignant progression. Effective implementation of that strategy has been hampered by difficulties in clearly distinguishing cystic lesions with no malignant potential from those with malignant potential. Here we explored whether glycosylation variants on specific proteins in cyst fluid samples could serve as biomarkers to aid in this diagnosis. METHODS: We used a novel antibody-lectin sandwich microarray method to measure the protein expression and glycosylation of mucin (MUC)1, MUC5AC, MUC16, carcinoembryonic antigen, and other proteins implicated in pancreatic neoplasia in cyst fluid samples. Fifty-three cyst fluid samples were obtained from patients with mucinous cystic neoplasms (n = 17), intraductal papillary mucinous neoplasms (n = 15), serous cystadenomas (n = 12), or pseudocysts (n = 9), with confirmation of histologic diagnosis at surgical resection. RESULTS: The detection of a glycan variant on MUC5AC using the lectin wheat-germ agglutinin discriminated mucin-producing cystic tumors (mucinous cystic neoplasms + intraductal papillary mucinous neoplasms) from benign cystic lesions (serous cystadenomas + pseudocysts) with a 78% sensitivity at 80% specificity, and when used in combination with cyst fluid CA 19-9 gave a sensitivity of 87% at 86% specificity. These biomarkers performed better than cyst fluid carcinoembryonic antigen (37%/80% sensitivity/specificity). CONCLUSIONS: These results demonstrate the value of glycan variants for biomarker discovery and suggest that these biomarkers could greatly enhance the accuracy of differentiating pancreatic cystic tumors. Validation studies will be required to determine the clinical value of these markers.

Original languageEnglish
Pages (from-to)937-945
Number of pages9
JournalAnnals of Surgery
Volume251
Issue number5
DOIs
StatePublished - May 2010

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Mucins
Pancreatic Neoplasms
Glycosylation
Cyst Fluid
Biomarkers
Neoplasms
Serous Cystadenoma
Carcinoembryonic Antigen
Lectins
Polysaccharides
Mucin-1
Wheat Germ Agglutinins
Validation Studies
Cysts
Pancreas
Proteins
Sensitivity and Specificity
Antibodies

ASJC Scopus subject areas

  • Surgery

Cite this

Haab, B. B., Porter, A., Yue, T., Li, L., Scheiman, J., Anderson, M. A., ... Simeone, D. M. (2010). Glycosylation variants of mucins and CEACAMs as candidate biomarkers for the diagnosis of pancreatic cystic neoplasms. Annals of Surgery, 251(5), 937-945. https://doi.org/10.1097/SLA.0b013e3181d7738d

Glycosylation variants of mucins and CEACAMs as candidate biomarkers for the diagnosis of pancreatic cystic neoplasms. / Haab, Brian B.; Porter, Andrew; Yue, Tingting; Li, Lin; Scheiman, James; Anderson, Michelle A.; Barnes, Dawn; Schmidt, C.; Feng, Ziding; Simeone, Diane M.

In: Annals of Surgery, Vol. 251, No. 5, 05.2010, p. 937-945.

Research output: Contribution to journalArticle

Haab, BB, Porter, A, Yue, T, Li, L, Scheiman, J, Anderson, MA, Barnes, D, Schmidt, C, Feng, Z & Simeone, DM 2010, 'Glycosylation variants of mucins and CEACAMs as candidate biomarkers for the diagnosis of pancreatic cystic neoplasms', Annals of Surgery, vol. 251, no. 5, pp. 937-945. https://doi.org/10.1097/SLA.0b013e3181d7738d
Haab, Brian B. ; Porter, Andrew ; Yue, Tingting ; Li, Lin ; Scheiman, James ; Anderson, Michelle A. ; Barnes, Dawn ; Schmidt, C. ; Feng, Ziding ; Simeone, Diane M. / Glycosylation variants of mucins and CEACAMs as candidate biomarkers for the diagnosis of pancreatic cystic neoplasms. In: Annals of Surgery. 2010 ; Vol. 251, No. 5. pp. 937-945.
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abstract = "BACKGROUND AND AIMS: Cystic lesions of the pancreas are increasingly being recognized due to the widespread use of high resolution abdominal imaging. Since certain cyst types are precursors to invasive cancer, this situation presents an opportunity to intervene prior to malignant progression. Effective implementation of that strategy has been hampered by difficulties in clearly distinguishing cystic lesions with no malignant potential from those with malignant potential. Here we explored whether glycosylation variants on specific proteins in cyst fluid samples could serve as biomarkers to aid in this diagnosis. METHODS: We used a novel antibody-lectin sandwich microarray method to measure the protein expression and glycosylation of mucin (MUC)1, MUC5AC, MUC16, carcinoembryonic antigen, and other proteins implicated in pancreatic neoplasia in cyst fluid samples. Fifty-three cyst fluid samples were obtained from patients with mucinous cystic neoplasms (n = 17), intraductal papillary mucinous neoplasms (n = 15), serous cystadenomas (n = 12), or pseudocysts (n = 9), with confirmation of histologic diagnosis at surgical resection. RESULTS: The detection of a glycan variant on MUC5AC using the lectin wheat-germ agglutinin discriminated mucin-producing cystic tumors (mucinous cystic neoplasms + intraductal papillary mucinous neoplasms) from benign cystic lesions (serous cystadenomas + pseudocysts) with a 78{\%} sensitivity at 80{\%} specificity, and when used in combination with cyst fluid CA 19-9 gave a sensitivity of 87{\%} at 86{\%} specificity. These biomarkers performed better than cyst fluid carcinoembryonic antigen (37{\%}/80{\%} sensitivity/specificity). CONCLUSIONS: These results demonstrate the value of glycan variants for biomarker discovery and suggest that these biomarkers could greatly enhance the accuracy of differentiating pancreatic cystic tumors. Validation studies will be required to determine the clinical value of these markers.",
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AU - Porter, Andrew

AU - Yue, Tingting

AU - Li, Lin

AU - Scheiman, James

AU - Anderson, Michelle A.

AU - Barnes, Dawn

AU - Schmidt, C.

AU - Feng, Ziding

AU - Simeone, Diane M.

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AB - BACKGROUND AND AIMS: Cystic lesions of the pancreas are increasingly being recognized due to the widespread use of high resolution abdominal imaging. Since certain cyst types are precursors to invasive cancer, this situation presents an opportunity to intervene prior to malignant progression. Effective implementation of that strategy has been hampered by difficulties in clearly distinguishing cystic lesions with no malignant potential from those with malignant potential. Here we explored whether glycosylation variants on specific proteins in cyst fluid samples could serve as biomarkers to aid in this diagnosis. METHODS: We used a novel antibody-lectin sandwich microarray method to measure the protein expression and glycosylation of mucin (MUC)1, MUC5AC, MUC16, carcinoembryonic antigen, and other proteins implicated in pancreatic neoplasia in cyst fluid samples. Fifty-three cyst fluid samples were obtained from patients with mucinous cystic neoplasms (n = 17), intraductal papillary mucinous neoplasms (n = 15), serous cystadenomas (n = 12), or pseudocysts (n = 9), with confirmation of histologic diagnosis at surgical resection. RESULTS: The detection of a glycan variant on MUC5AC using the lectin wheat-germ agglutinin discriminated mucin-producing cystic tumors (mucinous cystic neoplasms + intraductal papillary mucinous neoplasms) from benign cystic lesions (serous cystadenomas + pseudocysts) with a 78% sensitivity at 80% specificity, and when used in combination with cyst fluid CA 19-9 gave a sensitivity of 87% at 86% specificity. These biomarkers performed better than cyst fluid carcinoembryonic antigen (37%/80% sensitivity/specificity). CONCLUSIONS: These results demonstrate the value of glycan variants for biomarker discovery and suggest that these biomarkers could greatly enhance the accuracy of differentiating pancreatic cystic tumors. Validation studies will be required to determine the clinical value of these markers.

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