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N-Glycomic Profiling of Pheochromocytomas and Paragangliomas Separates Metastatic and Nonmetastatic Disease

Abstract Context No effective methods for separating primary pheochromocytomas and paragangliomas with metastatic potential are currently available. The identification of specific asparagine-linked glycan (N-glycan) structures, which are associated with metastasized pheochromocytomas and paraganglio... Full description

Journal Title: The journal of clinical endocrinology and metabolism 2017-11, Vol.102 (11), p.3990-4000
Main Author: Leijon, Helena
Other Authors: Kaprio, Tuomas , Heiskanen, Annamari , Satomaa, Tero , Hiltunen, Jukka O , Miettinen, Markku M , Arola, Johanna , Haglund, Caj
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: Washington, DC: Endocrine Society
ID: ISSN: 0021-972X
Link: https://www.ncbi.nlm.nih.gov/pubmed/28938401
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title: N-Glycomic Profiling of Pheochromocytomas and Paragangliomas Separates Metastatic and Nonmetastatic Disease
format: Article
creator:
  • Leijon, Helena
  • Kaprio, Tuomas
  • Heiskanen, Annamari
  • Satomaa, Tero
  • Hiltunen, Jukka O
  • Miettinen, Markku M
  • Arola, Johanna
  • Haglund, Caj
subjects:
  • Abridged Index Medicus
  • Adrenal Gland Neoplasms - diagnosis
  • Adrenal Gland Neoplasms - metabolism
  • Adrenal Gland Neoplasms - pathology
  • Adult
  • Aged
  • Asparagine
  • Cancer
  • carbohydrates (lipids)
  • Clinical Research Articles
  • Clinical s
  • Desorption
  • Diagnosis, Differential
  • Diagnostic software
  • Editor's Choice
  • endocrine system
  • endocrine system diseases
  • Female
  • Glycan
  • Glycomics
  • Glycosylation
  • Humans
  • Ionization
  • Ions
  • Male
  • Malignancy
  • Mannose
  • Mass spectrometry
  • Mass spectroscopy
  • Metastases
  • Metastasis
  • Middle Aged
  • N-Acetylglucosamine
  • Neoplasm Metastasis
  • Neoplasm Staging - methods
  • Paraffin
  • Paraganglioma
  • Paraganglioma - diagnosis
  • Paraganglioma - metabolism
  • Paraganglioma - pathology
  • Pheochromocytoma - diagnosis
  • Pheochromocytoma - metabolism
  • Pheochromocytoma - pathology
  • Polysaccharides
  • Polysaccharides - metabolism
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Tumors
  • Young Adult
ispartof: The journal of clinical endocrinology and metabolism, 2017-11, Vol.102 (11), p.3990-4000
description: Abstract Context No effective methods for separating primary pheochromocytomas and paragangliomas with metastatic potential are currently available. The identification of specific asparagine-linked glycan (N-glycan) structures, which are associated with metastasized pheochromocytomas and paragangliomas, may serve as a diagnostic tool. Objective To identify differences in N-glycomic profiles of primary metastasized and nonmetastasized pheochromocytomas and paragangliomas. Setting This study was conducted at Helsinki University Hospital, University of Helsinki, and Glykos Finland Ltd. and included 16 pheochromocytomas and paragangliomas: 8 primary metastasized pheochromocytomas or paragangliomas and 8 nonmetastasized tumors. Methods N-glycan structures were analyzed with matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) profiling of formalin-fixed, paraffin-embedded tissue samples. Main Outcome Measure N-glycan profile of tumor tissue. Results Four groups of neutral N-glycan signals were more abundant in metastasized tumors than in nonmetastasized tumors: complex-type N-glycan signals of cancer-associated terminal N-acetylglucosamine, multifucosylated glycans (complex fucosylation), hybrid-type N-glycans, and fucosylated pauci-mannose-type N-glycans. Three groups of acidic N-glycans were more abundant in metastasized tumors: multifucosylated glycans, acid ester–modified (sulfated or phosphorylated) glycans, and hybrid-type/monoantennary N-glycans. Fucosylation and complex fucosylation were significantly more abundant in metastasized paragangliomas and pheochromocytomas than in nonmetastasized tumors for individual tests but were over the false positivity critical rate, when adjusted for multiplicity testing. Conclusions MALDI-TOF MS profiling of primary pheochromocytomas and paragangliomas can identify diseases with metastatic potential based on their different N-glycan profiles. Thus, malignancy-linked N-glycan structures may serve as potential diagnostic tools for pheochromocytomas and paragangliomas. MALDI-TOF MS profiling of primary metastasized and nonmetastasized pheochromocytomas and paragangliomas identified differences between their N-glycan profiles.
language: eng
source:
identifier: ISSN: 0021-972X
fulltext: no_fulltext
issn:
  • 0021-972X
  • 1945-7197
url: Link


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titleN-Glycomic Profiling of Pheochromocytomas and Paragangliomas Separates Metastatic and Nonmetastatic Disease
creatorLeijon, Helena ; Kaprio, Tuomas ; Heiskanen, Annamari ; Satomaa, Tero ; Hiltunen, Jukka O ; Miettinen, Markku M ; Arola, Johanna ; Haglund, Caj
creatorcontribLeijon, Helena ; Kaprio, Tuomas ; Heiskanen, Annamari ; Satomaa, Tero ; Hiltunen, Jukka O ; Miettinen, Markku M ; Arola, Johanna ; Haglund, Caj
descriptionAbstract Context No effective methods for separating primary pheochromocytomas and paragangliomas with metastatic potential are currently available. The identification of specific asparagine-linked glycan (N-glycan) structures, which are associated with metastasized pheochromocytomas and paragangliomas, may serve as a diagnostic tool. Objective To identify differences in N-glycomic profiles of primary metastasized and nonmetastasized pheochromocytomas and paragangliomas. Setting This study was conducted at Helsinki University Hospital, University of Helsinki, and Glykos Finland Ltd. and included 16 pheochromocytomas and paragangliomas: 8 primary metastasized pheochromocytomas or paragangliomas and 8 nonmetastasized tumors. Methods N-glycan structures were analyzed with matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) profiling of formalin-fixed, paraffin-embedded tissue samples. Main Outcome Measure N-glycan profile of tumor tissue. Results Four groups of neutral N-glycan signals were more abundant in metastasized tumors than in nonmetastasized tumors: complex-type N-glycan signals of cancer-associated terminal N-acetylglucosamine, multifucosylated glycans (complex fucosylation), hybrid-type N-glycans, and fucosylated pauci-mannose-type N-glycans. Three groups of acidic N-glycans were more abundant in metastasized tumors: multifucosylated glycans, acid ester–modified (sulfated or phosphorylated) glycans, and hybrid-type/monoantennary N-glycans. Fucosylation and complex fucosylation were significantly more abundant in metastasized paragangliomas and pheochromocytomas than in nonmetastasized tumors for individual tests but were over the false positivity critical rate, when adjusted for multiplicity testing. Conclusions MALDI-TOF MS profiling of primary pheochromocytomas and paragangliomas can identify diseases with metastatic potential based on their different N-glycan profiles. Thus, malignancy-linked N-glycan structures may serve as potential diagnostic tools for pheochromocytomas and paragangliomas. MALDI-TOF MS profiling of primary metastasized and nonmetastasized pheochromocytomas and paragangliomas identified differences between their N-glycan profiles.
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1EISSN: 1945-7197
2DOI: 10.1210/jc.2017-00401
3PMID: 28938401
languageeng
publisherWashington, DC: Endocrine Society
subjectAbridged Index Medicus ; Adrenal Gland Neoplasms - diagnosis ; Adrenal Gland Neoplasms - metabolism ; Adrenal Gland Neoplasms - pathology ; Adult ; Aged ; Asparagine ; Cancer ; carbohydrates (lipids) ; Clinical Research Articles ; Clinical s ; Desorption ; Diagnosis, Differential ; Diagnostic software ; Editor's Choice ; endocrine system ; endocrine system diseases ; Female ; Glycan ; Glycomics ; Glycosylation ; Humans ; Ionization ; Ions ; Male ; Malignancy ; Mannose ; Mass spectrometry ; Mass spectroscopy ; Metastases ; Metastasis ; Middle Aged ; N-Acetylglucosamine ; Neoplasm Metastasis ; Neoplasm Staging - methods ; Paraffin ; Paraganglioma ; Paraganglioma - diagnosis ; Paraganglioma - metabolism ; Paraganglioma - pathology ; Pheochromocytoma - diagnosis ; Pheochromocytoma - metabolism ; Pheochromocytoma - pathology ; Polysaccharides ; Polysaccharides - metabolism ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Tumors ; Young Adult
ispartofThe journal of clinical endocrinology and metabolism, 2017-11, Vol.102 (11), p.3990-4000
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0Leijon, Helena
1Kaprio, Tuomas
2Heiskanen, Annamari
3Satomaa, Tero
4Hiltunen, Jukka O
5Miettinen, Markku M
6Arola, Johanna
7Haglund, Caj
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0N-Glycomic Profiling of Pheochromocytomas and Paragangliomas Separates Metastatic and Nonmetastatic Disease
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descriptionAbstract Context No effective methods for separating primary pheochromocytomas and paragangliomas with metastatic potential are currently available. The identification of specific asparagine-linked glycan (N-glycan) structures, which are associated with metastasized pheochromocytomas and paragangliomas, may serve as a diagnostic tool. Objective To identify differences in N-glycomic profiles of primary metastasized and nonmetastasized pheochromocytomas and paragangliomas. Setting This study was conducted at Helsinki University Hospital, University of Helsinki, and Glykos Finland Ltd. and included 16 pheochromocytomas and paragangliomas: 8 primary metastasized pheochromocytomas or paragangliomas and 8 nonmetastasized tumors. Methods N-glycan structures were analyzed with matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) profiling of formalin-fixed, paraffin-embedded tissue samples. Main Outcome Measure N-glycan profile of tumor tissue. Results Four groups of neutral N-glycan signals were more abundant in metastasized tumors than in nonmetastasized tumors: complex-type N-glycan signals of cancer-associated terminal N-acetylglucosamine, multifucosylated glycans (complex fucosylation), hybrid-type N-glycans, and fucosylated pauci-mannose-type N-glycans. Three groups of acidic N-glycans were more abundant in metastasized tumors: multifucosylated glycans, acid ester–modified (sulfated or phosphorylated) glycans, and hybrid-type/monoantennary N-glycans. Fucosylation and complex fucosylation were significantly more abundant in metastasized paragangliomas and pheochromocytomas than in nonmetastasized tumors for individual tests but were over the false positivity critical rate, when adjusted for multiplicity testing. Conclusions MALDI-TOF MS profiling of primary pheochromocytomas and paragangliomas can identify diseases with metastatic potential based on their different N-glycan profiles. Thus, malignancy-linked N-glycan structures may serve as potential diagnostic tools for pheochromocytomas and paragangliomas. MALDI-TOF MS profiling of primary metastasized and nonmetastasized pheochromocytomas and paragangliomas identified differences between their N-glycan profiles.
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0Abridged Index Medicus
1Adrenal Gland Neoplasms - diagnosis
2Adrenal Gland Neoplasms - metabolism
3Adrenal Gland Neoplasms - pathology
4Adult
5Aged
6Asparagine
7Cancer
8carbohydrates (lipids)
9Clinical Research Articles
10Clinical s
11Desorption
12Diagnosis, Differential
13Diagnostic software
14Editor's Choice
15endocrine system
16endocrine system diseases
17Female
18Glycan
19Glycomics
20Glycosylation
21Humans
22Ionization
23Ions
24Male
25Malignancy
26Mannose
27Mass spectrometry
28Mass spectroscopy
29Metastases
30Metastasis
31Middle Aged
32N-Acetylglucosamine
33Neoplasm Metastasis
34Neoplasm Staging - methods
35Paraffin
36Paraganglioma
37Paraganglioma - diagnosis
38Paraganglioma - metabolism
39Paraganglioma - pathology
40Pheochromocytoma - diagnosis
41Pheochromocytoma - metabolism
42Pheochromocytoma - pathology
43Polysaccharides
44Polysaccharides - metabolism
45Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
46Tumors
47Young Adult
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titleN-Glycomic Profiling of Pheochromocytomas and Paragangliomas Separates Metastatic and Nonmetastatic Disease
authorLeijon, Helena ; Kaprio, Tuomas ; Heiskanen, Annamari ; Satomaa, Tero ; Hiltunen, Jukka O ; Miettinen, Markku M ; Arola, Johanna ; Haglund, Caj
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0Abridged Index Medicus
1Adrenal Gland Neoplasms - diagnosis
2Adrenal Gland Neoplasms - metabolism
3Adrenal Gland Neoplasms - pathology
4Adult
5Aged
6Asparagine
7Cancer
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10Clinical s
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12Diagnosis, Differential
13Diagnostic software
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16endocrine system diseases
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19Glycomics
20Glycosylation
21Humans
22Ionization
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25Malignancy
26Mannose
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31Middle Aged
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38Paraganglioma - metabolism
39Paraganglioma - pathology
40Pheochromocytoma - diagnosis
41Pheochromocytoma - metabolism
42Pheochromocytoma - pathology
43Polysaccharides
44Polysaccharides - metabolism
45Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
46Tumors
47Young Adult
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date2017-11
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volume102
issue11
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pages3990-4000
issn0021-972X
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notesThese authors contributed equally to this study.
abstractAbstract Context No effective methods for separating primary pheochromocytomas and paragangliomas with metastatic potential are currently available. The identification of specific asparagine-linked glycan (N-glycan) structures, which are associated with metastasized pheochromocytomas and paragangliomas, may serve as a diagnostic tool. Objective To identify differences in N-glycomic profiles of primary metastasized and nonmetastasized pheochromocytomas and paragangliomas. Setting This study was conducted at Helsinki University Hospital, University of Helsinki, and Glykos Finland Ltd. and included 16 pheochromocytomas and paragangliomas: 8 primary metastasized pheochromocytomas or paragangliomas and 8 nonmetastasized tumors. Methods N-glycan structures were analyzed with matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) profiling of formalin-fixed, paraffin-embedded tissue samples. Main Outcome Measure N-glycan profile of tumor tissue. Results Four groups of neutral N-glycan signals were more abundant in metastasized tumors than in nonmetastasized tumors: complex-type N-glycan signals of cancer-associated terminal N-acetylglucosamine, multifucosylated glycans (complex fucosylation), hybrid-type N-glycans, and fucosylated pauci-mannose-type N-glycans. Three groups of acidic N-glycans were more abundant in metastasized tumors: multifucosylated glycans, acid ester–modified (sulfated or phosphorylated) glycans, and hybrid-type/monoantennary N-glycans. Fucosylation and complex fucosylation were significantly more abundant in metastasized paragangliomas and pheochromocytomas than in nonmetastasized tumors for individual tests but were over the false positivity critical rate, when adjusted for multiplicity testing. Conclusions MALDI-TOF MS profiling of primary pheochromocytomas and paragangliomas can identify diseases with metastatic potential based on their different N-glycan profiles. Thus, malignancy-linked N-glycan structures may serve as potential diagnostic tools for pheochromocytomas and paragangliomas. MALDI-TOF MS profiling of primary metastasized and nonmetastasized pheochromocytomas and paragangliomas identified differences between their N-glycan profiles.
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