A novel biomarker of fibrofatty replacement in dystrophinopathies identified by integrating transcriptome, magnetic resonance imaging, and pathology data

Autor: Zhihao Xie, Chang Liu, Chengyue Sun, Yanyu Lu, Shiyi Wu, Yilin Liu, Qi Wang, Yalan Wan, Yikang Wang, Meng Yu, Lingchao Meng, Jianwen Deng, Wei Zhang, Zhaoxia Wang, Chunxia Yang, Yun Yuan, Zhiying Xie
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Journal of Cachexia, Sarcopenia and Muscle, Vol 15, Iss 1, Pp 98-111 (2024)
Druh dokumentu: article
ISSN: 2190-6009
2190-5991
DOI: 10.1002/jcsm.13410
Popis: Abstract Background We aimed to analyse genome‐wide transcriptome differences between Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) patients and identify biomarkers that correlate well with muscle magnetic resonance imaging (MRI) and histological fibrofatty replacement in both patients, which have not been reported. Methods One hundred and one male patients with dystrophinopathies (55 DMD and 46 BMD) were enrolled. Muscle‐derived genome‐wide RNA‐sequencing was performed in 31 DMD patients, 29 BMD patients, and 11 normal controls. Fibrofatty replacement was scored on muscle MRI and histological levels in all patients. A unique pipeline, single‐sample gene set enrichment analysis combined with Spearman's rank correlations (ssGSEA‐Cor) was developed to identify the most correlated gene signature for fibrofatty replacement. Quantitative real‐time PCR (qRT‐PCR) analysis, western blot analysis, and single‐nucleus RNA‐sequencing (snRNA‐seq) were performed in the remaining patients to validate the most correlated gene signature. Results Comparative transcriptomic analysis revealed that 31 DMD muscles were characterized by a significant increase of inflammation/immune response and extracellular matrix remodelling compared with 29 BMD muscles (P
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