Murakami, M.* ; Sun, N. ; Li, F. ; Feuchtinger, A. ; Gomez-Sanchez, C.* ; Fassnacht, M.* ; Reincke, M.* ; Bancos, I.* ; Walch, A.K. ; Kroiss, M.* ; Beuschlein, F.*
In situ metabolomics of cortisol-producing adenomas.
Clin. Chem. 69, 149-159 (2023)
BACKGROUND: Recent advances in omics techniques have allowed detailed genetic characterization of cortisol-producing adrenal adenoma (CPA). In contrast, the pathophysiology of CPAs has not been elucidated in detail on the level of tumor metabolic alterations. METHODS: The current study conducted a comprehensive mass spectrometry imaging (MSI) map of CPAs in relation to clinical phenotypes and immunohistochemical profiles of steroidogenic enzymes. The study cohort comprised 46 patients with adrenal tumors including CPAs (n = 35) and nonfunctional adenomas (n = 11). RESULTS: Severity of cortisol hypersecretion was significantly correlated with 29 metabolites (adjusted P < 0.05). Adrenal androgens derived from the classic androgen pathway were inversely correlated with both cortisol secretion (rs = -0.41, adjusted P = 0.035) and CYP11B1 expression (rs = -0.77, adjusted P = 2.00E-08). The extent of cortisol excess and tumor CYP11B1 expression further correlated with serotonin (rs = 0.48 and 0.62, adjusted P = 0.008 and 2.41E-05). Tumor size was found to be correlated with abundance of 13 fatty acids (adjusted P < 0.05) and negatively associated with 9 polyunsaturated fatty acids including phosphatidic acid 38:8 (rs = -0.56, adjusted P = 0.009). CONCLUSIONS: MSI reveals novel metabolic links between endocrine function and tumorigenesis, which will further support the understanding of CPA pathophysiology.
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Publication type
Article: Journal article
Document type
Scientific Article
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Editors
Keywords
Cushing Syndrome ; Adrenal Adenoma ; Cortisol ; Metabolome ; Steroidogenic Enzyme; Mass-spectrometry; Adrenal Incidentalomas; Patterns
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Language
english
Publication Year
2023
Prepublished in Year
2022
HGF-reported in Year
2022
ISSN (print) / ISBN
0009-9147
e-ISSN
1530-8561
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Volume: 69,
Issue: 2,
Pages: 149-159
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American Association for Clinical Chemistry
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Journals Dept, 2001 Evans Rd, Cary, Nc 27513 Usa
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Reviewing status
Peer reviewed
POF-Topic(s)
30205 - Bioengineering and Digital Health
30202 - Environmental Health
Research field(s)
Enabling and Novel Technologies
PSP Element(s)
G-500390-001
A-630600-001
Grants
NIDDK NIH HHS
NIH HHS
Copyright
Erfassungsdatum
2023-01-16