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Dynamic gene expressions of peripheral blood mononuclear cells in patients with acute exacerbation of chronic obstructive pulmonary disease: a preliminary study.

Wu X, Sun X, Chen C, Bai C, Wang X - Crit Care (2014)

Bottom Line: We found that 14 genes were co-differentially upregulated and 2 downregulated greater than 10-fold in patients with COPD or AECOPD compared with the healthy individuals.Dynamic changes of Aminolevulinate-delta-synthase 2 and carbonic anhydrase I had similar patterns of Digital Evaluation Score System scores and may serve as potential genes of interest during the course of AECOPD.Thus, our findings indicate a panel of altered gene expression patterns in PBMCs that can be used as AECOPD-specific dynamic biomarkers to monitor the course of AECOPD.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Fenglin Rd. No180, 200032, Shanghai, China. physicianwuxd@126.com.

ABSTRACT

Introduction: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a serious event that is responsible for the progress of the disease, increases in medical costs and high mortality.

Methods: The aim of the present study was to identify AECOPD-specific biomarkers by evaluating the dynamic gene expression profiling of peripheral blood mononuclear cells (PBMCs) from patients with AECOPD on days 1, 3 and 10 after hospital admission and to compare the derived data with data from healthy controls or patients with stable COPD.

Results: We found that 14 genes were co-differentially upregulated and 2 downregulated greater than 10-fold in patients with COPD or AECOPD compared with the healthy individuals. Eight co-differentially upregulated genes and six downregulated genes were identified as a panel of AECOPD-specific genes. Downregulation of TCF7 in PBMCs was found to be associated with the severity of COPD. Dynamic changes of Aminolevulinate-delta-synthase 2 and carbonic anhydrase I had similar patterns of Digital Evaluation Score System scores and may serve as potential genes of interest during the course of AECOPD.

Conclusion: Thus, our findings indicate a panel of altered gene expression patterns in PBMCs that can be used as AECOPD-specific dynamic biomarkers to monitor the course of AECOPD.

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Related in: MedlinePlus

Gene expression profile comparisons regarding the cellular component. Graphs describe co–differentially upregulated genes (A) or downregulated genes (B) in the cellular component of peripheral blood mononuclear cells from patients with chronic obstructive pulmonary disease (COPD), including stable COPD and acute exacerbation of COPD (AECOPD), as compared to healthy control subjects. Also shown are co–differentially expressed upregulated genes (C) or downregulated genes (D) from patients with AECOPD, as compared to both patients with stable COPD and healthy control subjects. MHC, Major histocompatibility complex.
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Fig5: Gene expression profile comparisons regarding the cellular component. Graphs describe co–differentially upregulated genes (A) or downregulated genes (B) in the cellular component of peripheral blood mononuclear cells from patients with chronic obstructive pulmonary disease (COPD), including stable COPD and acute exacerbation of COPD (AECOPD), as compared to healthy control subjects. Also shown are co–differentially expressed upregulated genes (C) or downregulated genes (D) from patients with AECOPD, as compared to both patients with stable COPD and healthy control subjects. MHC, Major histocompatibility complex.

Mentions: In the biological process, COPD-specific upregulated genes were involved mainly in peptide cross-linking, blood vessel development, biological adhesion or cell adhesion (Figure 4A). COPD-specific downregulated genes were involved mainly in T cell receptor signaling pathways, antigen receptor–mediated signaling pathways, immune response–activating cell surface receptor signaling pathways or steroid biosynthetic process (Figure 4B). AECOPD-specific genes upregulated in response to organic substance, response to wounding, multicellular organismal process or response to chemical stimulus are shown in Figure 4C. AECOPD-specific downregulated genes were involved mainly in the regulation of immune response and the immune system process or in the immune response and immune system process themselves (Figure 4D). In the cellular component, COPD-specific upregulated genes were involved mainly in the extracellular region, the extracellular matrix part, the proteinaceous extracellular matrix or the extracellular matrix (Figure 5A). COPD-specific downregulated genes were involved mainly in the major histocompatibility complex class II (MHC II) protein complex, microbody lumen, peroxisomal matrix or MHC II protein complex (Figure 5B). AECOPD-specific upregulated genes were involved mainly in the extracellular region part, the extracellular matrix, the extracellular space or the extracellular region (Figure 5C). AECOPD-specific downregulated genes were involved mainly in the cell periphery and the plasma membrane and were integral to the plasma membrane and intrinsic to the plasma membrane (Figure 5D). In molecular function, COPD-specific upregulated genes participated mainly in extracellular matrix structural constituent, platelet-derived growth factor binding, serine-type endopeptidase activity and protein binding (Figure 6A). COPD-specific downregulated genes were involved mainly in nucleoside kinase activity, MHC class II receptor activity, C-acyltransferase activity and ephrin receptor activity (Figure 6B). AECOPD-specific upregulated genes were involved mainly in protein binding, growth factor binding, calcium ion binding and polysaccharide binding (Figure 6C). AECOPD-specific downregulated genes were involved mainly in receptor activity, signaling receptor activity, molecular transducer activity and signal transducer activity (Figure 6D).Figure 4


Dynamic gene expressions of peripheral blood mononuclear cells in patients with acute exacerbation of chronic obstructive pulmonary disease: a preliminary study.

Wu X, Sun X, Chen C, Bai C, Wang X - Crit Care (2014)

Gene expression profile comparisons regarding the cellular component. Graphs describe co–differentially upregulated genes (A) or downregulated genes (B) in the cellular component of peripheral blood mononuclear cells from patients with chronic obstructive pulmonary disease (COPD), including stable COPD and acute exacerbation of COPD (AECOPD), as compared to healthy control subjects. Also shown are co–differentially expressed upregulated genes (C) or downregulated genes (D) from patients with AECOPD, as compared to both patients with stable COPD and healthy control subjects. MHC, Major histocompatibility complex.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4305227&req=5

Fig5: Gene expression profile comparisons regarding the cellular component. Graphs describe co–differentially upregulated genes (A) or downregulated genes (B) in the cellular component of peripheral blood mononuclear cells from patients with chronic obstructive pulmonary disease (COPD), including stable COPD and acute exacerbation of COPD (AECOPD), as compared to healthy control subjects. Also shown are co–differentially expressed upregulated genes (C) or downregulated genes (D) from patients with AECOPD, as compared to both patients with stable COPD and healthy control subjects. MHC, Major histocompatibility complex.
Mentions: In the biological process, COPD-specific upregulated genes were involved mainly in peptide cross-linking, blood vessel development, biological adhesion or cell adhesion (Figure 4A). COPD-specific downregulated genes were involved mainly in T cell receptor signaling pathways, antigen receptor–mediated signaling pathways, immune response–activating cell surface receptor signaling pathways or steroid biosynthetic process (Figure 4B). AECOPD-specific genes upregulated in response to organic substance, response to wounding, multicellular organismal process or response to chemical stimulus are shown in Figure 4C. AECOPD-specific downregulated genes were involved mainly in the regulation of immune response and the immune system process or in the immune response and immune system process themselves (Figure 4D). In the cellular component, COPD-specific upregulated genes were involved mainly in the extracellular region, the extracellular matrix part, the proteinaceous extracellular matrix or the extracellular matrix (Figure 5A). COPD-specific downregulated genes were involved mainly in the major histocompatibility complex class II (MHC II) protein complex, microbody lumen, peroxisomal matrix or MHC II protein complex (Figure 5B). AECOPD-specific upregulated genes were involved mainly in the extracellular region part, the extracellular matrix, the extracellular space or the extracellular region (Figure 5C). AECOPD-specific downregulated genes were involved mainly in the cell periphery and the plasma membrane and were integral to the plasma membrane and intrinsic to the plasma membrane (Figure 5D). In molecular function, COPD-specific upregulated genes participated mainly in extracellular matrix structural constituent, platelet-derived growth factor binding, serine-type endopeptidase activity and protein binding (Figure 6A). COPD-specific downregulated genes were involved mainly in nucleoside kinase activity, MHC class II receptor activity, C-acyltransferase activity and ephrin receptor activity (Figure 6B). AECOPD-specific upregulated genes were involved mainly in protein binding, growth factor binding, calcium ion binding and polysaccharide binding (Figure 6C). AECOPD-specific downregulated genes were involved mainly in receptor activity, signaling receptor activity, molecular transducer activity and signal transducer activity (Figure 6D).Figure 4

Bottom Line: We found that 14 genes were co-differentially upregulated and 2 downregulated greater than 10-fold in patients with COPD or AECOPD compared with the healthy individuals.Dynamic changes of Aminolevulinate-delta-synthase 2 and carbonic anhydrase I had similar patterns of Digital Evaluation Score System scores and may serve as potential genes of interest during the course of AECOPD.Thus, our findings indicate a panel of altered gene expression patterns in PBMCs that can be used as AECOPD-specific dynamic biomarkers to monitor the course of AECOPD.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Fenglin Rd. No180, 200032, Shanghai, China. physicianwuxd@126.com.

ABSTRACT

Introduction: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a serious event that is responsible for the progress of the disease, increases in medical costs and high mortality.

Methods: The aim of the present study was to identify AECOPD-specific biomarkers by evaluating the dynamic gene expression profiling of peripheral blood mononuclear cells (PBMCs) from patients with AECOPD on days 1, 3 and 10 after hospital admission and to compare the derived data with data from healthy controls or patients with stable COPD.

Results: We found that 14 genes were co-differentially upregulated and 2 downregulated greater than 10-fold in patients with COPD or AECOPD compared with the healthy individuals. Eight co-differentially upregulated genes and six downregulated genes were identified as a panel of AECOPD-specific genes. Downregulation of TCF7 in PBMCs was found to be associated with the severity of COPD. Dynamic changes of Aminolevulinate-delta-synthase 2 and carbonic anhydrase I had similar patterns of Digital Evaluation Score System scores and may serve as potential genes of interest during the course of AECOPD.

Conclusion: Thus, our findings indicate a panel of altered gene expression patterns in PBMCs that can be used as AECOPD-specific dynamic biomarkers to monitor the course of AECOPD.

Show MeSH
Related in: MedlinePlus