Peripheral Blood Mononuclear Cell Gene Expression Profiles May Predict Poor Outcome in Idiopathic Pulmonary Fibrosis
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ABSTRACT:
PROVIDER: PRJNA139675 | ENA |
REPOSITORIES: ENA
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Project description:Background: In this study we aimed to identify peripheral blood mononuclear cell (PBMC) gene expression profiles predictive of poor outcomes in idiopathic pulmonary fibrosis (IPF) Methods: Microarray analyses of PBMC were performed in 120 patients from discovery (n=45) and replication cohorts (n=75). Genes and pathways associated with transplant-free survival (TFS) were identified and confirmed by qRT-PCR. Findings: 52 genes were predictive of TFS in a discovery cohort (FDR<5%, Cox score above 2.5 or below -2.5). Clustering the replication cohort samples using these genes distinguished two patient groups with significantly different TFS (hazard ratio 1.96, 95%CI 1.01-3.8, P=0.018). Decreased expression of M-bM-^@M-^\The co-stimulatory signaling during T cell activationM-bM-^@M-^] Biocarta pathway and in particular CD28, ICOS, LCK and ITK was associated with shorter TFS times in each cohort (FDR<5%). qRT-PCR expression of CD28, ICOS, LCK and ITK correlated with the microarray results in the discovery cohort (P<0.05) and their decreased expression was predictive of shorter TFS in the replication cohort (P<0.05). A genomic and clinical model demonstrated an area under the ROC curve of 78.5% at 2.4 months for death and lung transplant prediction. Interpretation: Our results suggest that CD28, ICOS, LCK and ITK are outcome biomarkers in IPF. PBMC from 75 patients with the diagnosis of IPF were obtained within 30 minutes from blood draw. Total RNA was extracted, labeled and hybridized to Agilent Whole Human Genome Oligo Microarray, 4 x 44K. Patients were followed from blood draw until death, transplant or last follow up. Hierarchical clustering and gene-set analysis with censored outcome data were used to study the association of gene expression and outcome in this cohort (replication cohort)
2013-10-15 | E-GEOD-28042 | biostudies-arrayexpress
Project description:Background: In this study we aimed to identify peripheral blood mononuclear cell (PBMC) gene expression profiles predictive of poor outcomes in idiopathic pulmonary fibrosis (IPF) Methods: Microarray analyses of PBMC were performed in 120 patients from discovery (n=45) and replication cohorts (n=75). Genes and pathways associated with transplant-free survival (TFS) were identified and confirmed by qRT-PCR. Findings: 52 genes were predictive of TFS in a discovery cohort (FDR<5%, Cox score above 2.5 or below -2.5). Clustering the replication cohort samples using these genes distinguished two patient groups with significantly different TFS (hazard ratio 1.96, 95%CI 1.01-3.8, P=0.018). Decreased expression of “The co-stimulatory signaling during T cell activation” Biocarta pathway and in particular CD28, ICOS, LCK and ITK was associated with shorter TFS times in each cohort (FDR<5%). qRT-PCR expression of CD28, ICOS, LCK and ITK correlated with the microarray results in the discovery cohort (P<0.05) and their decreased expression was predictive of shorter TFS in the replication cohort (P<0.05). A genomic and clinical model demonstrated an area under the ROC curve of 78.5% at 2.4 months for death and lung transplant prediction. Interpretation: Our results suggest that CD28, ICOS, LCK and ITK are outcome biomarkers in IPF.
2013-10-15 | GSE28221 | GEO
Project description:Background: In this study we aimed to identify peripheral blood mononuclear cell (PBMC) gene expression profiles predictive of poor outcomes in idiopathic pulmonary fibrosis (IPF) Methods: Microarray analyses of PBMC were performed in 120 patients from discovery (n=45) and replication cohorts (n=75). Genes and pathways associated with transplant-free survival (TFS) were identified and confirmed by qRT-PCR. Findings: 52 genes were predictive of TFS in a discovery cohort (FDR<5%, Cox score above 2.5 or below -2.5). Clustering the replication cohort samples using these genes distinguished two patient groups with significantly different TFS (hazard ratio 1.96, 95%CI 1.01-3.8, P=0.018). Decreased expression of M-bM-^@M-^\The co-stimulatory signaling during T cell activationM-bM-^@M-^] Biocarta pathway and in particular CD28, ICOS, LCK and ITK was associated with shorter TFS times in each cohort (FDR<5%). qRT-PCR expression of CD28, ICOS, LCK and ITK correlated with the microarray results in the discovery cohort (P<0.05) and their decreased expression was predictive of shorter TFS in the replication cohort (P<0.05). A genomic and clinical model demonstrated an area under the ROC curve of 78.5% at 2.4 months for death and lung transplant prediction. Interpretation: Our results suggest that CD28, ICOS, LCK and ITK are outcome biomarkers in IPF. The 'GeneID_matched_gene_expression_dataset_of_IPF_cohorts.txt' supplementary data file contains the matched gene expression data of the subseries GSE28042 with the subseries GSE27957 by gene ID (details in the readme.txt) This SuperSeries is composed of the SubSeries listed below.
2013-10-15 | E-GEOD-28221 | biostudies-arrayexpress
Project description:Background: In this study we aimed to identify peripheral blood mononuclear cell (PBMC) gene expression profiles predictive of poor outcomes in idiopathic pulmonary fibrosis (IPF) Methods: Microarray analyses of PBMC were performed in 120 patients from discovery (n=45) and replication cohorts (n=75). Genes and pathways associated with transplant-free survival (TFS) were identified and confirmed by qRT-PCR. Findings: 52 genes were predictive of TFS in a discovery cohort (FDR<5%, Cox score above 2.5 or below -2.5). Clustering the replication cohort samples using these genes distinguished two patient groups with significantly different TFS (hazard ratio 1.96, 95%CI 1.01-3.8, P=0.018). Decreased expression of M-bM-^@M-^\The co-stimulatory signaling during T cell activationM-bM-^@M-^] Biocarta pathway and in particular CD28, ICOS, LCK and ITK was associated with shorter TFS times in each cohort (FDR<5%). qRT-PCR expression of CD28, ICOS, LCK and ITK correlated with the microarray results in the discovery cohort (P<0.05) and their decreased expression was predictive of shorter TFS in the replication cohort (P<0.05). A genomic and clinical model demonstrated an area under the ROC curve of 78.5% at 2.4 months for death and lung transplant prediction. Interpretation: Our results suggest that CD28, ICOS, LCK and ITK are outcome biomarkers in IPF. They should be further evaluated for patient prioritization for lung transplantation and stratification in drug studies. This submission represents the Affymetrix component of the study (discovery cohort)
2013-10-15 | E-GEOD-27957 | biostudies-arrayexpress
Project description:Background: In this study we aimed to identify peripheral blood mononuclear cell (PBMC) gene expression profiles predictive of poor outcomes in idiopathic pulmonary fibrosis (IPF) Methods: Microarray analyses of PBMC were performed in 120 patients from discovery (n=45) and replication cohorts (n=75). Genes and pathways associated with transplant-free survival (TFS) were identified and confirmed by qRT-PCR. Findings: 52 genes were predictive of TFS in a discovery cohort (FDR<5%, Cox score above 2.5 or below -2.5). Clustering the replication cohort samples using these genes distinguished two patient groups with significantly different TFS (hazard ratio 1.96, 95%CI 1.01-3.8, P=0.018). Decreased expression of “The co-stimulatory signaling during T cell activation” Biocarta pathway and in particular CD28, ICOS, LCK and ITK was associated with shorter TFS times in each cohort (FDR<5%). qRT-PCR expression of CD28, ICOS, LCK and ITK correlated with the microarray results in the discovery cohort (P<0.05) and their decreased expression was predictive of shorter TFS in the replication cohort (P<0.05). A genomic and clinical model demonstrated an area under the ROC curve of 78.5% at 2.4 months for death and lung transplant prediction. Interpretation: Our results suggest that CD28, ICOS, LCK and ITK are outcome biomarkers in IPF.
2013-10-15 | GSE28042 | GEO
Project description:Background: In this study we aimed to identify peripheral blood mononuclear cell (PBMC) gene expression profiles predictive of poor outcomes in idiopathic pulmonary fibrosis (IPF) Methods: Microarray analyses of PBMC were performed in 120 patients from discovery (n=45) and replication cohorts (n=75). Genes and pathways associated with transplant-free survival (TFS) were identified and confirmed by qRT-PCR. Findings: 52 genes were predictive of TFS in a discovery cohort (FDR<5%, Cox score above 2.5 or below -2.5). Clustering the replication cohort samples using these genes distinguished two patient groups with significantly different TFS (hazard ratio 1.96, 95%CI 1.01-3.8, P=0.018). Decreased expression of “The co-stimulatory signaling during T cell activation” Biocarta pathway and in particular CD28, ICOS, LCK and ITK was associated with shorter TFS times in each cohort (FDR<5%). qRT-PCR expression of CD28, ICOS, LCK and ITK correlated with the microarray results in the discovery cohort (P<0.05) and their decreased expression was predictive of shorter TFS in the replication cohort (P<0.05). A genomic and clinical model demonstrated an area under the ROC curve of 78.5% at 2.4 months for death and lung transplant prediction. Interpretation: Our results suggest that CD28, ICOS, LCK and ITK are outcome biomarkers in IPF. They should be further evaluated for patient prioritization for lung transplantation and stratification in drug studies.
2013-10-15 | GSE27957 | GEO
Project description:We aimed to identify peripheral blood mononuclear cell (PBMC) gene expression profiles predictive of poor outcomes in idiopathic pulmonary fibrosis (IPF) by performing microarray experiments of PBMCs in discovery and replication cohorts of IPF patients. Microarray analyses identified 52 genes associated with transplant-free survival (TFS) in the discovery cohort. Clustering the microarray samples of the replication cohort using the 52-gene outcome-predictive signature distinguished two patient groups with significant differences in TFS. We studied the pathways associated with TFS in each independent microarray cohort and identified decreased expression of "The costimulatory signal during T cell activation" Biocarta pathway and, in particular, the genes CD28, ICOS, LCK, and ITK, results confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). A proportional hazards model, including the qRT-PCR expression of CD28, ICOS, LCK, and ITK along with patient's age, gender, and percent predicted forced vital capacity (FVC%), demonstrated an area under the receiver operating characteristic curve of 78.5% at 2.4 months for death and lung transplant prediction in the replication cohort. To evaluate the potential cellular source of CD28, ICOS, LCK, and ITK expression, we analyzed and found significant correlation of these genes with the PBMC percentage of CD4(+)CD28(+) T cells in the replication cohort. Our results suggest that CD28, ICOS, LCK, and ITK are potential outcome biomarkers in IPF and should be further evaluated for patient prioritization for lung transplantation and stratification in drug studies.
| S-EPMC4175518 | biostudies-literature
Project description:Peripheral Blood Mononuclear Cell Gene Expression Profiles May Predict Poor Outcome in Idiopathic Pulmonary Fibrosis [Agilent]
| PRJNA141911 | ENA
Project description:Peripheral Blood Mononuclear Cell Gene Expression Profiles May Predict Poor Outcome in Idiopathic Pulmonary Fibrosis [Affymetrix]
| PRJNA141927 | ENA
Project description:Prediction of outcome for melanoma patients with surgically-resected macroscopic nodal metastases is very imprecise. We performed a comprehensive clinicopathologic assessment of fresh-frozen macroscopic nodal metastases and the preceding primary melanoma, somatic mutation profiling and gene expression profiling to identify determinants of outcome in 79 melanoma patients. In addition to disease stage <II at initial presentation, the following clinical and pathologic factors were independent predictors of improved outcome (ORs for survival >4yr, 90%CI): presence of a nodular component in the primary melanoma (6.8, 0.6-76.0), and small cell size (11.1, 0.8-100.0) or low pigmentation (3.0, 0.8-100.0) in the nodal metastases. Absence of BRAF mutation (20.0, 1.0-1000.0) or NRAS mutation (16.7, 0.6-1000.0) were both favourable prognostic factors. A 46-gene expression signature with strong over-representation of immune response genes was predictive of better survival (10.9, 0.4-325.6); in the full cohort median survival was >100 months in those with the signature, but 10 months in those without. This relationship was validated in two previously published independent stage III melanoma datasets. We conclude that the presence of BRAF mutation, NRAS mutation and absence of an immune-related expressed gene profile predict poor outcome in melanoma patients with macroscopic stage III disease.
2013-12-10 | GSE53118 | GEO