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BAL cell gene expression is predictive of Mortality in Idiopathic Pulmonary Fibrosis and enriched for Genes of Airway Basal Cells

ABSTRACT: BAL cell gene expression is predictive of Mortality in Idiopathic Pulmonary Fibrosis and enriched for Genes of Airway Basal Cells

PROVIDER: PRJNA289721 | ENA |

REPOSITORIES: ENA

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BAL cell gene expression is predictive of Mortality in Idiopathic Pulmonary Fibrosis and enriched for Genes of Airway Basal Cells (II)

Project description:Background: Idiopathic pulmonary fibrosis (IPF) is a fatal disease with variable outcome. Currently, there is little information whether changes in molecular pathways in the alveolar compartment of patients with IPF are indicative of disease progression. To address this question we analyzed gene expression signatures in cells obtained from bronchoalveolar lavage (BAL) of patients with IPF. Methods: BAL cells were harvested from 212 IPF patients and 20 healthy donors at the time of diagnosis. RNA was extracted, labeled and hybridized to Agilent gene expression arrays. Our study included a discovery cohort of 62 patients from Freiburg, Germany, and two independent validation cohorts, Siena, Italy (50 patients) and Leuven, Belgium (64 patients). Survival analysis was performed by applying Cox models and component-wise boosting. Results: We found 1582 genes predictive of mortality in the discovery cohort in univariate analyses adjusted for age and gender at FDR<0.05. A nine gene signature, developed by component-wise boosting in the Freiburg array dataset, performed well in both validation cohorts, Siena (p<0.0032) and Leuven (p=0.0033). The genes associated with mortality in BAL cells were significantly enriched for genes expressed in airway basal epithelial cells, airway progenitor cells recently implicated in fibrosis. Conclusions: Our results identify and validate a BAL cell gene expression signature that predicts mortality in IPF. This signature unmasks a potential novel role for airway basal epithelial cells in IPF.

2018-12-31 | GSE70866 | GEO

BAL cell gene expression is predictive of Mortality in Idiopathic Pulmonary Fibrosis and enriched for Genes of Airway Basal Cells (III)

Project description:Background: We got interested whether genes of airway basal cells are enriched in sarcoidosis. Methods: Bronchoscopy with bronchoalveolar lavage (BAL) was performed in 26 patients with sarcoidosis, chest-x-ray type III and IV, and 20 healthy donors and isolated BAL cells.Transcriptome of BAL cells were studied by using Affymetrix Human Affymetrix Whole-Transcript Human Gene 1.0 ST array on an Affymetrix platform. Microarray data were imported, log2-transformed and quantile normalized using robust multi-array average (RMA). We tested enrichment for airway basal cells by global enrichment analysis. Results: we did not find enrichment of airway basal cell genes in sarcoidosis compared to healthy volunteers.

2018-12-31 | GSE73394 | GEO

BAL cell gene expression is predictive of Mortality in Idiopathic Pulmonary Fibrosis and enriched for Genes of Airway Basal Cells (IV)

Project description:Background: We got interested whether genes of airway basal cells are enriched in COPD. Methods: Bronchoscopy with bronchial brushes and bronchoalveolar lavage was performed in 28 patients with COPD and 29 healthy donors and isolated BAL cells.Transcriptome of BAL cells were studied by using Affymetrix Human Genome U133 Plus 2.0 array on an Affymetrix platform. Microarray data were normalized data were imported, log2-transformed and quantile normalized using robust multi-array average (RMA). We tested enrichment for airway basal cells by ROMER enrichment analysis. Results: we did not find enrichment of airway basal cell genes in COPD compared to healthy volunteers.

2018-12-31 | GSE73395 | GEO

BAL cell gene expression is predictive of Mortality in Idiopathic Pulmonary Fibrosis and enriched for Genes of Airway Basal Cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-12-31 | GSE70867 | GEO

BAL cell gene expression is predictive of Mortality in Idiopathic Pulmonary Fibrosis and enriched for Genes of Airway Basal Cells (I)

Project description:Background: Based on previous publication and our own data we became interested in the gene expression signature of airway basal cells. Methods: Bronchoscopy with bronchial brushes and bronchoalveolar lavage was performed in healthy donors. Airway basal cells were obtained by brushing segmental bronchi of the right lower lobe and outgrowth of cells in BEGM supplemented with growth factors according to the manufacturer’s instructions. Alveolar macrophages were sorted by flow cytometry. Microarray data of 11 airway basal cell samples, 7 alveolar macrophage samples and 4 samples of bronchial epithelial cells were obtained. The transcriptome of the three different cell types was compared using univariate ANOVA resulting in 8874 genes significantly differently expressed between the three cell types (p<0.0001). The data of these 8874 transcripts were used for a clustering approach applying Cluster 3.0 software. The samples were hierarchically clustered with median normalization of the genes and centroid linkage, and the similarity metric used was Pearson correlation. Results and Conclusion: we obtained an airway basal cell type specific signature consisting out of 961 genes which was used in further studies.

2018-12-31 | GSE70864 | GEO

CXCL13 is a predictive biomarker in idiopathic multicentric Castleman disease

Project description:CXCL13 is a predictive biomarker in idiopathic multicentric Castleman disease

| PRJNA898421 | ENA

A role for complement in idiopathic pulmonary fibrosis

Project description:The pathogenesis of idiopathic pulmonary fibrosis is multifactorial and characterized by progressive fibrosis and excessive accumulation of extracellular matrix in the interstitium of the lung, and driven by an imbalance between anti-fibrotic and pro-fibrotic factors leading to collagen deposition. In the present study we wanted to identify proteins involved in these processes, and performed high-resolution proteomic profiling of bronchoalveolar lavage (BAL) from IPF patients and controls. The proteomic analysis of BAL demonstrated that the complement system was highly differentially regulated in IPF patients as compared with controls.

2023-07-31 | PXD036638 | Pride

CXCL13 is a predictive biomarker in idiopathic multicentric Castleman disease

Project description:Idiopathic multicentric Castleman disease (iMCD) is a rare and poorly-understood cytokine storm-driven inflammatory disorder. Interleukin-6 (IL-6) is a known disease driver in some patients, but anti-IL-6 therapy with siltuximab is not effective in all patients, and biomarkers indicating success at an early time point following treatment initiation are lacking. Here we show, by comparison of levels of 1,178 proteins in sera of healthy participants (N=42), patients with iMCD (N=88), and with related diseases (N=60), a comprehensive landscape of candidate disease mediators and predictors of siltuximab response. C-X-C Motif Chemokine Ligand-13 (CXCL13) is identified and validated as the protein most prominently up-regulated in iMCD. Early and significant decrease in CXCL13 levels clearly distinguishes siltuximab responders from non-responders; a 17% reduction by day 8 following siltuximab therapy initiation is predictive of response at later time points. Our study thus suggests that CXCL13 is a predictive biomarker of response to siltuximab in iMCD.

2022-11-04 | GSE217351 | GEO

BAL proteomic signature of lung adenocarcinoma in IPF patients and its transposition in serum samples for less invasive diagnostic procedures

Project description:Idiopathic pulmonary fibrosis (IPF) is a form of chronic and irreversible fibrosing interstitial pneumonia of unknown aetiology, with an average survival time of 3-5 years after diagnosis. Emerging evidence suggests that IPF increases the risk of lung carcinogenesis. Both diseases show similarities in terms of risk factors, such as history of smoking, concomitant emphysema, and viral infections, besides sharing similar pathogenic pathways. Lung cancer diagnosis is often difficult in IPF patients because of the diffuse lung injuries and abnormalities due to the underlying fibrosis. This is reflected in the lack of optimal therapeutic strategies for patients with both diseases. For this purpose, we performed a proteomic study on bronchoalveolar lavage (BAL) samples from IPF, LC associated with IPF (LC-IPF) patients, and healthy controls (CTRL). Molecular pathways involved in inflammation, immune response, lipid metabolism and cell adhesion were found for the dysregulated proteins in LC-IPF, of which TTHY, APOA1, S10A9, RET4, GDRI1 and PROF1. The correlation test revealed a relationship between inflammation-related proteins and proteins associated with lipid metabolism. Also, the up-regulation of PROF1 in LC-IPF BAL and S10A9 in LC-IPF serum was validated. While APOA1 and APOE were validated as highly abundant in IPF BAL and low abundant in IPF serum. We evaluated nicotinamide phosphoribosyltransferase levels in serum highlighting its down-regulation in LC-IPF. Our retrospective analyses on BAL of IPF and LC-IPF patients extrapolate some potential biomarkers whose further evaluation at the serum level, permits the measurement of these potential biomarkers with a less invasive procedure.

2023-03-11 | PXD037720 | Pride

human BAL metagenome

Project description:human BAL metagenome Raw sequence reads

| PRJNA835222 | ENA