Background: A central issue hindering the development of effective anti-fibrosis drugs for heart failure is the unclear interrelationship between fibrosis and the immune cells. This study aims at providing precise subtyping of heart failure based on immune cell fractions, elaborating their differences in fibrotic mechanisms, and proposing a biomarker panel for evaluating intrinsic features of patients' physiological statuses through subtype classification, thereby promoting the precision medicine for cardiac fibrosis.
Methods: We inferred immune cell type abundance of the ventricular samples by a computational method (CIBERSORTx) based on ventricular tissue samples from 103 patients with heart failure, and applied K-means clustering to divide patients into two subtypes based on their immune cell type abundance. We also designed a novel analytic strategy: Large-Scale Functional Score and Association Analysis (LAFSAA), to study fibrotic mechanisms in the two subtypes.
Results: Two subtypes of immune cell fractions: pro-inflammatory and pro-remodeling subtypes, were identified. LAFSAA identified 11 subtype-specific pro-fibrotic functional gene sets as the basis for personalised targeted treatments. Based on feature selection, a 30-gene biomarker panel (ImmunCard30) established for diagnosing patient subtypes achieved high classification performance, with the area under the receiver operator characteristic curve corresponding to 0.954 and 0.803 for the discovery and validation sets, respectively.
Conclusion: Patients with the two subtypes of cardiac immune cell fractions were likely having different fibrotic mechanisms. Patients' subtypes can be predicted based on the ImmunCard30 biomarker panel. We envision that our unique stratification strategy revealed in this study will unravel advance diagnostic techniques for personalised anti-fibrotic therapy.
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http://dx.doi.org/10.3389/fimmu.2023.1053793 | DOI Listing |
Cell Signal
December 2024
Department of Maxillofacial and Otorhinolaryngology Oncology and Department of Head and Neck Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China; Tianjin Key Laboratory of Basic and Translational Medicine on Head & Neck Cancer, Tianjin, China; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China. Electronic address:
Nerves are often overlooked as key components of the tumor microenvironment. However, the molecular mechanisms underlying the reciprocal interactions between tumors and nerves remain largely unknown. In this study, we analyzed data from The Cancer Genome Atlas (TCGA) and identified a significant association between DKK1 expression and poor prognosis, as well as a correlation between DKK1 expression and myeloid-derived suppressor cell (MDSC) infiltration in head and neck squamous cell carcinoma (HNSCC) and pancreatic ductal adenocarcinoma (PDAC), two cancer types characterized by pronounced tumor-nerve interactions.
View Article and Find Full Text PDFMol Neurobiol
December 2024
Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, 150000, Heilongjiang, China.
Ferroptosis and autophagy are closely associated with Alzheimer's disease (AD). Elevated ferric ion levels can induce oxidative stress and chronic inflammatory responses, resulting in brain tissue damage and further neurological cell damage. Autophagy in Alzheimer's has a dual role.
View Article and Find Full Text PDFNat Cancer
December 2024
Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
The cerebrospinal fluid (CSF) border accommodates diverse immune cells that permit peripheral cell immunosurveillance. However, the intricate interactions between CSF immune cells and infiltrating cancer cells remain poorly understood. Here we use fate mapping, longitudinal time-lapse imaging and multiomics technologies to investigate the precise origin, cellular crosstalk and molecular landscape of macrophages that contribute to leptomeningeal metastasis (LM) progression.
View Article and Find Full Text PDFEur J Med Res
December 2024
Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Shandong University, Jinan, 250021, Shandong, China.
The gut microbiota is a complex and dynamic ecosystem that plays a crucial role in human health and disease, including obesity, diabetes, cardiovascular diseases, neurodegenerative diseases, inflammatory bowel disease, and cancer. Chronic inflammation is a common feature of these diseases and is closely related to angiogenesis (the process of forming new blood vessels), which is often dysregulated in pathological conditions. Inflammation potentially acts as a central mediator.
View Article and Find Full Text PDFEur J Med Res
December 2024
Department of Ophthalmology, Zhongshan City People's Hospital, Zhongshan, Guangdong, China.
Background: Age-related macular degeneration (AMD), is a neurodegenerative ocular disease. This study investigated the role of ferroptosis-related genes and their interaction with immune cell infiltration in AMD.
Methods: We screened differential expression genes (DEGs) of AMD from data sets in Gene Expression Omnibus.
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