Investigating the biomarker potential of glycoproteins using comparative glycoprofiling - application to tissue inhibitor of metalloproteinases-1.

Morten Thaysen-Andersen; Ida Thøgersen; Ulrik Axel Lademann; Hanne Kjær Offenberg; Anders Giessing; Jan J. Enghild; Hans Jørgen Nielsen; Nils Brunner; Peter Højrup; Morten Thaysen-Andersen; Ida B Thøgersen; Ulrik Lademann; Hanne Offenberg; Anders M B Giessing; Jan J Enghild; Hans Jørgen Nielsen; Nils Brünner; Peter Højrup

doi:10.1016/j.bbapap.2007.12.007

Investigating the biomarker potential of glycoproteins using comparative glycoprofiling - application to tissue inhibitor of metalloproteinases-1.

Morten Thaysen-Andersen, Ida Thøgersen, Ulrik Axel Lademann, Hanne Kjær Offenberg, Anders Giessing, Jan J. Enghild, Hans Jørgen Nielsen, Nils Brunner, Peter Højrup, Morten Thaysen-Andersen, Ida B Thøgersen, Ulrik Lademann, Hanne Offenberg, Anders M B Giessing, Jan J Enghild, Hans Jørgen Nielsen, Nils Brünner, Peter Højrup

Department of Clinical Medicine

30 Citations (Scopus)

Abstract

Cancer-induced alterations of protein glycosylations are well-known phenomena. Hence, the glycoprofile of certain glycoproteins can potentially be used as biomarkers for early diagnosis. However, there are a substantial number of candidates and the techniques for measuring their biomarker potential are limited, calling for new methods. Here, we have investigated the cancer marker potential of the glycoprofile of tissue inhibitor of metalloproteinase-1 (TIMP-1) using a method for comparative glycoprofiling. Glycoprofiles were obtained from plasma TIMP-1 of five healthy donors and five colorectal cancer (CRC) patients showing increased amounts of TIMP-1. Furthermore, the TIMP-1 glycoprofiles of media from two colon cancer cell lines (CCC) and a prostate cancer cell line were determined as disease references. TIMP-1 was purified from IgG-depleted samples using immuno affinity and gel electrophoresis and the glycoprofiling was performed using glycopeptide enrichment and mass spectrometry. The heterogeneous glycoprofiles of TIMP-1 were found to be highly conserved among the healthy donors, proving an ideal candidate marker and showed high reproducibility of the method. Numerous CCC-specific TIMP-1 glycans were observed illustrating cancer-induced changes. Unexpectedly, quantitation revealed that the glycoprofiles of healthy donors and CRC patients varied minimally. Considering the increased CRC TIMP-1 levels and the observed CCC-specific glycans, the lack of variation indicates that the increased amount of CRC TIMP-1 is not a direct product of the cancer cells. Hence, the TIMP-1 glycoprofile holds no biomarker potential for CRC when using plasma as the sample origin. This study clearly illustrates that the technique is capable of performing individualised site-specific glycan analysis and representing a new tool for biomarker investigation of low-abundant glycoproteins.

Original language	English
Journal	BBA General Subjects
Volume	1784
Issue number	3
Pages (from-to)	455-63
Number of pages	8
ISSN	0304-4165
DOIs	https://doi.org/10.1016/j.bbapap.2007.12.007 https://doi.org/10.1016/j.bbapap.2007.12.007
Publication status	Published - 2008

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Thaysen-Andersen, M., Thøgersen, I., Lademann, U. A., Offenberg, H. K., Giessing, A., Enghild, J. J., Nielsen, H. J., Brunner, N., Højrup, P., Thaysen-Andersen, M., Thøgersen, I. B., Lademann, U., Offenberg, H., Giessing, A. M. B., Enghild, J. J., Nielsen, H. J., Brünner, N., & Højrup, P. (2008). Investigating the biomarker potential of glycoproteins using comparative glycoprofiling - application to tissue inhibitor of metalloproteinases-1. BBA General Subjects, 1784(3), 455-63. https://doi.org/10.1016/j.bbapap.2007.12.007, https://doi.org/10.1016/j.bbapap.2007.12.007

Thaysen-Andersen, M, Thøgersen, I, Lademann, UA, Offenberg, HK, Giessing, A, Enghild, JJ, Nielsen, HJ, Brunner, N, Højrup, P, Thaysen-Andersen, M, Thøgersen, IB, Lademann, U, Offenberg, H, Giessing, AMB, Enghild, JJ, Nielsen, HJ, Brünner, N & Højrup, P 2008, 'Investigating the biomarker potential of glycoproteins using comparative glycoprofiling - application to tissue inhibitor of metalloproteinases-1.', BBA General Subjects, vol. 1784, no. 3, pp. 455-63. https://doi.org/10.1016/j.bbapap.2007.12.007, https://doi.org/10.1016/j.bbapap.2007.12.007

@article{a0a432f0c5de11dd9473000ea68e967b,

title = "Investigating the biomarker potential of glycoproteins using comparative glycoprofiling - application to tissue inhibitor of metalloproteinases-1.",

abstract = "Cancer-induced alterations of protein glycosylations are well-known phenomena. Hence, the glycoprofile of certain glycoproteins can potentially be used as biomarkers for early diagnosis. However, there are a substantial number of candidates and the techniques for measuring their biomarker potential are limited, calling for new methods. Here, we have investigated the cancer marker potential of the glycoprofile of tissue inhibitor of metalloproteinase-1 (TIMP-1) using a method for comparative glycoprofiling. Glycoprofiles were obtained from plasma TIMP-1 of five healthy donors and five colorectal cancer (CRC) patients showing increased amounts of TIMP-1. Furthermore, the TIMP-1 glycoprofiles of media from two colon cancer cell lines (CCC) and a prostate cancer cell line were determined as disease references. TIMP-1 was purified from IgG-depleted samples using immuno affinity and gel electrophoresis and the glycoprofiling was performed using glycopeptide enrichment and mass spectrometry. The heterogeneous glycoprofiles of TIMP-1 were found to be highly conserved among the healthy donors, proving an ideal candidate marker and showed high reproducibility of the method. Numerous CCC-specific TIMP-1 glycans were observed illustrating cancer-induced changes. Unexpectedly, quantitation revealed that the glycoprofiles of healthy donors and CRC patients varied minimally. Considering the increased CRC TIMP-1 levels and the observed CCC-specific glycans, the lack of variation indicates that the increased amount of CRC TIMP-1 is not a direct product of the cancer cells. Hence, the TIMP-1 glycoprofile holds no biomarker potential for CRC when using plasma as the sample origin. This study clearly illustrates that the technique is capable of performing individualised site-specific glycan analysis and representing a new tool for biomarker investigation of low-abundant glycoproteins.",

author = "Morten Thaysen-Andersen and Ida Th{\o}gersen and Lademann, {Ulrik Axel} and Offenberg, {Hanne Kj{\ae}r} and Anders Giessing and Enghild, {Jan J.} and Nielsen, {Hans J{\o}rgen} and Nils Brunner and Peter H{\o}jrup and Morten Thaysen-Andersen and Th{\o}gersen, {Ida B} and Ulrik Lademann and Hanne Offenberg and Giessing, {Anders M B} and Enghild, {Jan J} and Nielsen, {Hans J{\o}rgen} and Nils Br{\"u}nner and Peter H{\o}jrup",

note = "Keywords: Aged; Carbohydrate Sequence; Cell Line, Tumor; Colorectal Neoplasms; Female; Glycoproteins; Glycosylation; Humans; Male; Middle Aged; Molecular Sequence Data; Polysaccharides; Tissue Inhibitor of Metalloproteinase-1; Tumor Markers, Biological",

year = "2008",

doi = "10.1016/j.bbapap.2007.12.007",

language = "English",

volume = "1784",

pages = "455--63",

journal = "B B A - General Subjects",

issn = "0304-4165",

publisher = "Elsevier",

number = "3",

}

TY - JOUR

T1 - Investigating the biomarker potential of glycoproteins using comparative glycoprofiling - application to tissue inhibitor of metalloproteinases-1.

AU - Thaysen-Andersen, Morten

AU - Thøgersen, Ida

AU - Lademann, Ulrik Axel

AU - Offenberg, Hanne Kjær

AU - Giessing, Anders

AU - Enghild, Jan J.

AU - Nielsen, Hans Jørgen

AU - Brunner, Nils

AU - Højrup, Peter

AU - Thaysen-Andersen, Morten

AU - Thøgersen, Ida B

AU - Lademann, Ulrik

AU - Offenberg, Hanne

AU - Giessing, Anders M B

AU - Enghild, Jan J

AU - Nielsen, Hans Jørgen

AU - Brünner, Nils

AU - Højrup, Peter

N1 - Keywords: Aged; Carbohydrate Sequence; Cell Line, Tumor; Colorectal Neoplasms; Female; Glycoproteins; Glycosylation; Humans; Male; Middle Aged; Molecular Sequence Data; Polysaccharides; Tissue Inhibitor of Metalloproteinase-1; Tumor Markers, Biological

PY - 2008

Y1 - 2008

N2 - Cancer-induced alterations of protein glycosylations are well-known phenomena. Hence, the glycoprofile of certain glycoproteins can potentially be used as biomarkers for early diagnosis. However, there are a substantial number of candidates and the techniques for measuring their biomarker potential are limited, calling for new methods. Here, we have investigated the cancer marker potential of the glycoprofile of tissue inhibitor of metalloproteinase-1 (TIMP-1) using a method for comparative glycoprofiling. Glycoprofiles were obtained from plasma TIMP-1 of five healthy donors and five colorectal cancer (CRC) patients showing increased amounts of TIMP-1. Furthermore, the TIMP-1 glycoprofiles of media from two colon cancer cell lines (CCC) and a prostate cancer cell line were determined as disease references. TIMP-1 was purified from IgG-depleted samples using immuno affinity and gel electrophoresis and the glycoprofiling was performed using glycopeptide enrichment and mass spectrometry. The heterogeneous glycoprofiles of TIMP-1 were found to be highly conserved among the healthy donors, proving an ideal candidate marker and showed high reproducibility of the method. Numerous CCC-specific TIMP-1 glycans were observed illustrating cancer-induced changes. Unexpectedly, quantitation revealed that the glycoprofiles of healthy donors and CRC patients varied minimally. Considering the increased CRC TIMP-1 levels and the observed CCC-specific glycans, the lack of variation indicates that the increased amount of CRC TIMP-1 is not a direct product of the cancer cells. Hence, the TIMP-1 glycoprofile holds no biomarker potential for CRC when using plasma as the sample origin. This study clearly illustrates that the technique is capable of performing individualised site-specific glycan analysis and representing a new tool for biomarker investigation of low-abundant glycoproteins.

AB - Cancer-induced alterations of protein glycosylations are well-known phenomena. Hence, the glycoprofile of certain glycoproteins can potentially be used as biomarkers for early diagnosis. However, there are a substantial number of candidates and the techniques for measuring their biomarker potential are limited, calling for new methods. Here, we have investigated the cancer marker potential of the glycoprofile of tissue inhibitor of metalloproteinase-1 (TIMP-1) using a method for comparative glycoprofiling. Glycoprofiles were obtained from plasma TIMP-1 of five healthy donors and five colorectal cancer (CRC) patients showing increased amounts of TIMP-1. Furthermore, the TIMP-1 glycoprofiles of media from two colon cancer cell lines (CCC) and a prostate cancer cell line were determined as disease references. TIMP-1 was purified from IgG-depleted samples using immuno affinity and gel electrophoresis and the glycoprofiling was performed using glycopeptide enrichment and mass spectrometry. The heterogeneous glycoprofiles of TIMP-1 were found to be highly conserved among the healthy donors, proving an ideal candidate marker and showed high reproducibility of the method. Numerous CCC-specific TIMP-1 glycans were observed illustrating cancer-induced changes. Unexpectedly, quantitation revealed that the glycoprofiles of healthy donors and CRC patients varied minimally. Considering the increased CRC TIMP-1 levels and the observed CCC-specific glycans, the lack of variation indicates that the increased amount of CRC TIMP-1 is not a direct product of the cancer cells. Hence, the TIMP-1 glycoprofile holds no biomarker potential for CRC when using plasma as the sample origin. This study clearly illustrates that the technique is capable of performing individualised site-specific glycan analysis and representing a new tool for biomarker investigation of low-abundant glycoproteins.

U2 - 10.1016/j.bbapap.2007.12.007

DO - 10.1016/j.bbapap.2007.12.007

M3 - Journal article

C2 - 18206988

SN - 0304-4165

VL - 1784

SP - 455

EP - 463

JO - B B A - General Subjects

JF - B B A - General Subjects

IS - 3

ER -

Investigating the biomarker potential of glycoproteins using comparative glycoprofiling - application to tissue inhibitor of metalloproteinases-1.

Abstract

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