Dataset Information

Proteome Characterization of BALF Extracellular Vesicles in Idiopathic Pulmonary Fibrosis: Unveiling Undercover Molecular Pathways.

ABSTRACT: In the longtime challenge of identifying specific, easily detectable and reliable biomarkers of IPF, BALF proteomics is providing interesting new insights into its pathogenesis. To the best of our knowledge, the present study is the first shotgun proteomic investigation of EVs isolated from BALF of IPF patients. Our main aim was to characterize the proteome of the vesicular component of BALF and to explore its individual impact on the pathogenesis of IPF. To this purpose, ultracentrifugation was chosen as the EVs isolation technique, and their purification was assessed by TEM, 2DE and LC-MS/MS. Our 2DE data and scatter plots showed considerable differences between the proteome of EVs and that of whole BALF and of its fluid component. Analysis of protein content and protein functions evidenced that EV proteins are predominantly involved in cytoskeleton remodeling, adenosine signaling, adrenergic signaling, C-peptide signaling and lipid metabolism. Our findings may suggest a wider system involvement in the disease pathogenesis and support the importance of pre-fractioning of complex samples, such as BALF, in order to let low-abundant proteins-mediated pathways emerge.

SUBMITTER: Shaba E

PROVIDER: S-EPMC8199247 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Publications

Proteome Characterization of BALF Extracellular Vesicles in Idiopathic Pulmonary Fibrosis: Unveiling Undercover Molecular Pathways.

Shaba Enxhi E Landi Claudia C Carleo Alfonso A Vantaggiato Lorenza L Paccagnini Eugenio E Gentile Mariangela M Bianchi Laura L Lupetti Pietro P Bargagli Elena E Prasse Antje A Bini Luca L

International journal of molecular sciences 20210527 11

In the longtime challenge of identifying specific, easily detectable and reliable biomarkers of IPF, BALF proteomics is providing interesting new insights into its pathogenesis. To the best of our knowledge, the present study is the first shotgun proteomic investigation of EVs isolated from BALF of IPF patients. Our main aim was to characterize the proteome of the vesicular component of BALF and to explore its individual impact on the pathogenesis of IPF. To this purpose, ultracentrifugation was ...[more]

PMID: 34071777

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Project description:BackgroundIdiopathic pulmonary fibrosis (IPF) is a fatal heterogeneous disease with a varied clinical course that is difficult to predict. Accurate predictive models are urgently needed to identify individuals with poor survival for the optimal timing of referral for transplantation and provide some clues for mechanistic research on disease progression.MethodsWe obtained the gene expression profiles of bronchoalveolar lavage fluid (BALF) from the Gene Expression Omnibus. Individuals from the GPL14550 platform were assigned to the derivation cohort (n=112) and individuals from the GPL17077 platform to the validation cohort (n=64). Univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were applied to select candidate genes for overall survival. A nomogram model was constructed based on Cox hazard regression analysis. The model was assessed by C-statistic, calibration curve, and decision curve analysis (DCA) and was externally validated.ResultsA nomogram model comprising seven genes was constructed. Excellent discrimination and calibration were observed in the derivation (C-index 0.815) and validation (C-index 0.812) cohorts. The AUCs for predicting 1-, 2- and 3-year survival were 0.857, 0.918, 0.930 in the derivation cohort and 0.850, 0.880, 0.925 in the validation cohort, respectively. DCA confirmed the clinical applicability of the model. A risk score based on the model was an independent prognostic predictor and could divide patients into high- and low-risk groups. The Kaplan-Meier analysis displayed that high-risk patients exhibited significantly poorer survival compared with low-risk patients. Gene Set Enrichment Analysis (GSEA) showed that high-risk patients were primarily enriched in inflammatory hallmarks, and single sample GSEA (ssGSEA) indicated that the high-risk group is closely correlated with the immune process. These lead to increased insight into mechanisms associated with IPF progression that inflammation mediated by immune response might be involved in the disease progression.ConclusionsThe novel BALF seven-gene model performed well in risk stratification and individualized survival prediction for patients with IPF, facilitating personalized management of IPF patients. It deepened the understanding of the role of inflammation in IPF progression, which needs to be further studied.

Dataset Information

Proteome Characterization of BALF Extracellular Vesicles in Idiopathic Pulmonary Fibrosis: Unveiling Undercover Molecular Pathways.

Publications

Proteome Characterization of BALF Extracellular Vesicles in Idiopathic Pulmonary Fibrosis: Unveiling Undercover Molecular Pathways.

Similar Datasets

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