MicroRNA and metabolomics signatures for adrenomyeloneuropathy disease severity
Abstract Adrenomyeloneuropathy (AMN), the slow progressive phenotype of adrenoleukodystrophy (ALD), has no clinical plasma biomarker for disease progression. This feasibility study aimed to determine whether metabolomics and micro‐RNA in blood plasma provide a potential source of biomarkers for AMN...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-11-01
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| Series: | JIMD Reports |
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| Online Access: | https://doi.org/10.1002/jmd2.12323 |
| _version_ | 1797991043470196736 |
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| author | Bela Rui Turk Laila Marie Poisson Christina Linnea Nemeth Jordan Goodman Ann B. Moser Richard Owen Jones Ali Fatemi Jaspreet Singh |
| author_facet | Bela Rui Turk Laila Marie Poisson Christina Linnea Nemeth Jordan Goodman Ann B. Moser Richard Owen Jones Ali Fatemi Jaspreet Singh |
| author_sort | Bela Rui Turk |
| collection | DOAJ |
| description | Abstract Adrenomyeloneuropathy (AMN), the slow progressive phenotype of adrenoleukodystrophy (ALD), has no clinical plasma biomarker for disease progression. This feasibility study aimed to determine whether metabolomics and micro‐RNA in blood plasma provide a potential source of biomarkers for AMN disease severity. Metabolomics and RNA‐seq were performed on AMN and healthy human blood plasma. Biomarker discovery and pathway analyses were performed using clustering, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and regression against patient's clinical Expanded Disability Status Score (EDSS). Fourteen AMN and six healthy control samples were analyzed. AMN showed strong disease‐severity‐specific metabolic and miRNA clustering signatures. Strong, significant clinical correlations were shown for 7‐alpha‐hydroxy‐3‐oxo‐4‐cholestenoate (7‐HOCA) (r2 = 0.83, p < 0.00001), dehydroepiandrosterone sulfate (DHEA‐S; r2 = 0.82, p < 0.00001), hypoxanthine (r2 = 0.82, p < 0.00001), as well as miRNA‐432‐5p (r2 = 0.68, p < 0.00001). KEGG pathway comparison of mild versus severe disease identified affected downstream systems: GAREM, IGF‐1, CALCRL, SMAD2&3, glutathione peroxidase, LDH, and NOS. This feasibility study demonstrates that miRNA and metabolomics are a source of potential plasma biomarkers for disease severity in AMN, providing both a disease signature and individual markers with strong clinical correlations. Network analyses of affected systems implicate differentially altered vascular, inflammatory, and oxidative stress pathways, suggesting disease‐severity‐specific mechanisms as a function of disease severity. |
| first_indexed | 2024-04-11T08:46:12Z |
| format | Article |
| id | doaj.art-36123677d2714446a40c64bbf255f8ce |
| institution | Directory Open Access Journal |
| issn | 2192-8312 |
| language | English |
| last_indexed | 2024-04-11T08:46:12Z |
| publishDate | 2022-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | JIMD Reports |
| spelling | doaj.art-36123677d2714446a40c64bbf255f8ce2022-12-22T04:33:58ZengWileyJIMD Reports2192-83122022-11-0163659360310.1002/jmd2.12323MicroRNA and metabolomics signatures for adrenomyeloneuropathy disease severityBela Rui Turk0Laila Marie Poisson1Christina Linnea Nemeth2Jordan Goodman3Ann B. Moser4Richard Owen Jones5Ali Fatemi6Jaspreet Singh7Moser Center for Leukodystrophies, Kennedy Krieger Institute Johns Hopkins Medical Institutions Baltimore Maryland USADepartment of Public Health Sciences Henry Ford Health System Detroit Michigan USAMoser Center for Leukodystrophies, Kennedy Krieger Institute Johns Hopkins Medical Institutions Baltimore Maryland USAMoser Center for Leukodystrophies, Kennedy Krieger Institute Johns Hopkins Medical Institutions Baltimore Maryland USAMoser Center for Leukodystrophies, Kennedy Krieger Institute Johns Hopkins Medical Institutions Baltimore Maryland USAMoser Center for Leukodystrophies, Kennedy Krieger Institute Johns Hopkins Medical Institutions Baltimore Maryland USAMoser Center for Leukodystrophies, Kennedy Krieger Institute Johns Hopkins Medical Institutions Baltimore Maryland USADepartment of Neurology Henry Ford Health System Detroit Michigan USAAbstract Adrenomyeloneuropathy (AMN), the slow progressive phenotype of adrenoleukodystrophy (ALD), has no clinical plasma biomarker for disease progression. This feasibility study aimed to determine whether metabolomics and micro‐RNA in blood plasma provide a potential source of biomarkers for AMN disease severity. Metabolomics and RNA‐seq were performed on AMN and healthy human blood plasma. Biomarker discovery and pathway analyses were performed using clustering, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and regression against patient's clinical Expanded Disability Status Score (EDSS). Fourteen AMN and six healthy control samples were analyzed. AMN showed strong disease‐severity‐specific metabolic and miRNA clustering signatures. Strong, significant clinical correlations were shown for 7‐alpha‐hydroxy‐3‐oxo‐4‐cholestenoate (7‐HOCA) (r2 = 0.83, p < 0.00001), dehydroepiandrosterone sulfate (DHEA‐S; r2 = 0.82, p < 0.00001), hypoxanthine (r2 = 0.82, p < 0.00001), as well as miRNA‐432‐5p (r2 = 0.68, p < 0.00001). KEGG pathway comparison of mild versus severe disease identified affected downstream systems: GAREM, IGF‐1, CALCRL, SMAD2&3, glutathione peroxidase, LDH, and NOS. This feasibility study demonstrates that miRNA and metabolomics are a source of potential plasma biomarkers for disease severity in AMN, providing both a disease signature and individual markers with strong clinical correlations. Network analyses of affected systems implicate differentially altered vascular, inflammatory, and oxidative stress pathways, suggesting disease‐severity‐specific mechanisms as a function of disease severity.https://doi.org/10.1002/jmd2.12323adrenoleukodystrophyadrenomyeloneuropathybiomarkerleukodystrophymetabolomicsmicro‐RNA |
| spellingShingle | Bela Rui Turk Laila Marie Poisson Christina Linnea Nemeth Jordan Goodman Ann B. Moser Richard Owen Jones Ali Fatemi Jaspreet Singh MicroRNA and metabolomics signatures for adrenomyeloneuropathy disease severity JIMD Reports adrenoleukodystrophy adrenomyeloneuropathy biomarker leukodystrophy metabolomics micro‐RNA |
| title | MicroRNA and metabolomics signatures for adrenomyeloneuropathy disease severity |
| title_full | MicroRNA and metabolomics signatures for adrenomyeloneuropathy disease severity |
| title_fullStr | MicroRNA and metabolomics signatures for adrenomyeloneuropathy disease severity |
| title_full_unstemmed | MicroRNA and metabolomics signatures for adrenomyeloneuropathy disease severity |
| title_short | MicroRNA and metabolomics signatures for adrenomyeloneuropathy disease severity |
| title_sort | microrna and metabolomics signatures for adrenomyeloneuropathy disease severity |
| topic | adrenoleukodystrophy adrenomyeloneuropathy biomarker leukodystrophy metabolomics micro‐RNA |
| url | https://doi.org/10.1002/jmd2.12323 |
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