Inference of Cellular Immune Environments in Sputum and Peripheral Blood Associated with Acute Exacerbations of COPD

Norman, Katy C.; Freeman, Christine M.; Bidthanapally, Neha S; Han, MeiLan K.; Martínez, Fernando J.; Curtis, Jeffrey L.; Arnold, Kelly B.

doi:10.1007/s12195-019-00567-2

Cited by 4 publications

(3 citation statements)

References 57 publications

(69 reference statements)

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“…KEGG, analysis,showed that signal transduction, infectious diseases, immune system are the most signi cantly enriched pathways, which are closely related to in ammatory. Cellular immune environments and chemokines were considered as promising diagnostic and therapeutic targets in COPD [28,29]. Besides surgery, the in ammatory condition of COPD might limit the use of the programmed death 1 immune checkpoint inhibitor in lung cancer [30].…”

Section: Discussionmentioning

confidence: 99%

CircRNA Expression Profile in Lung Cancer Complicated with Chronic Obstructive Pulmonary Disease Patients

Wen¹,

Li²,

Shen³

et al. 2020

Preprint

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Background: Lung cancer complicated with chronic obstructive pulmonary disease (COPD) are major causes of mortality worldwide, and the incidence of lung cancer and COPD increasing significantly. Circular RNAs (circRNAs), have been reported to participate in various biological processes, whereas the role of circRNAs in lung cancer complicated with COPD remains unclear. We aims to identify differentially expressed circRNAs (DEcircRNAs) between lung cancer complicated with COPD and lung cancer without COPD. Method: The circRNAs expression profiles were identified using a high-throughput circRNA microarray in cancer adjacent tissues from 6 lung cancer without COPD patients and 8 lung cancer complicated with COPD patients. Bioinformatic analyses were conducted to identify the functions of DEcircRNAs. Result: A total of 115 up- and 128 down-regulated circRNAs were screened in lung cancer complicated with COPD patients compared with lung cancer without COPD patients. The myD88-dependent toll-like receptor signaling pathway and positive regulation of nitric oxide biosynthetic process ranked the top 2 enriched biological processes in Gene Ontology analysis. Signaling transduction and infectious diseases were the most significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways in both up- and down-regulated circRNAs. Compared with lung cancer without COPD, circRNAs are dysregulated in the adjacent tissues of lung cancer with COPD. Conclusion: The DEcircRNAs might act as potential targets for the diagnosis of lung cancer with COPD.

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Section: Discussionmentioning

confidence: 99%

CircRNA Expression Profile in Lung Cancer Complicated with Chronic Obstructive Pulmonary Disease Patients

Wen¹,

Li²,

Shen³

et al. 2020

Preprint

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“…These approaches have been successfully used to identify blood and bronchoalveolar lavage (BAL) protein signatures associated with disease state and progression in idiopathic pulmonary fibrosis 21 , 22 . We have also used them to integrate blood and sputum protein signatures associated with COPD exacerbation 23 .…”

Section: Introductionmentioning

confidence: 99%

A blood and bronchoalveolar lavage protein signature of rapid FEV1 decline in smoking-associated COPD

DiLillo¹,

Norman²,

Freeman³

et al. 2023

Sci Rep

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Accelerated progression of chronic obstructive pulmonary disease (COPD) is associated with increased risks of hospitalization and death. Prognostic insights into mechanisms and markers of progression could facilitate development of disease-modifying therapies. Although individual biomarkers exhibit some predictive value, performance is modest and their univariate nature limits network-level insights. To overcome these limitations and gain insights into early pathways associated with rapid progression, we measured 1305 peripheral blood and 48 bronchoalveolar lavage proteins in individuals with COPD [n = 45, mean initial forced expiratory volume in one second (FEV1) 75.6 ± 17.4% predicted]. We applied a data-driven analysis pipeline, which enabled identification of protein signatures that predicted individuals at-risk for accelerated lung function decline (FEV1 decline ≥ 70 mL/year) ~ 6 years later, with high accuracy. Progression signatures suggested that early dysregulation in elements of the complement cascade is associated with accelerated decline. Our results propose potential biomarkers and early aberrant signaling mechanisms driving rapid progression in COPD.

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“…Once identified and validated, these signatures may be used for diagnostic or prognostic purposes, or for generating new hypotheses for future experimental work. We have previously used these approaches to successfully identify a blood protein signature that differentiated healthy and IPF patients with high accuracy 26 , as well as signatures based on blood and sputum proteins and blood cell markers that differentiated stable and exacerbated chronic obstructive pulmonary disease (COPD) patients 27 .…”

mentioning

confidence: 99%

Identification of a unique temporal signature in blood and BAL associated with IPF progression

Norman

O’Dwyer

Salisbury

et al. 2020

Sci Rep

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Idiopathic pulmonary fibrosis (IPF) is a progressive and heterogeneous interstitial lung disease of unknown origin with a low survival rate. There are few treatment options available due to the fact that mechanisms underlying disease progression are not well understood, likely because they arise from dysregulation of complex signaling networks spanning multiple tissue compartments. To better characterize these networks, we used systems-focused data-driven modeling approaches to identify cross-tissue compartment (blood and bronchoalveolar lavage) and temporal proteomic signatures that differentiated IPF progressors and non-progressors. Partial least squares discriminant analysis identified a signature of 54 baseline (week 0) blood and lung proteins that differentiated IPF progression status by the end of 80 weeks of follow-up with 100% cross-validation accuracy. Overall we observed heterogeneous protein expression patterns in progressors compared to more homogenous signatures in non-progressors, and found that non-progressors were enriched for proteomic processes involving regulation of the immune/defense response. We also identified a temporal signature of blood proteins that was significantly different at early and late progressor time points (p < 0.0001), but not present in non-progressors. Overall, this approach can be used to generate new hypothesis for mechanisms associated with IPF progression and could readily be translated to other complex and heterogeneous diseases. Idiopathic pulmonary fibrosis (IPF) is a heterogeneous and irreversible interstitial pneumonia, with symptoms including progressive cough, shortness of breath, and ultimately respiratory failure, with a median survival of only 3-5 years post diagnosis 1. The disease is believed to be caused by a dysregulated wound healing response to various epithelial injuries leading to fibrosis of the lung interstitium 1. Two medications (nintedanib 2 and pirfenidone 3) are effective treatments for IPF; though neither can reverse the disease 4. Thus, lung transplantation is currently the only option for a cure 5 , even though this procedure has the highest failure rate of all organ transplantation options (54% at 5 years 6). Better understanding of mechanisms underpinning progression of pulmonary fibrosis could lead to improved outcomes via identification of new therapeutic targets. To add to the complexity surrounding IPF, disease progression is also heterogeneous, with some individual patients experiencing long-term stability and others rapid loss of lung function. A number of longitudinal cohort studies have been created with the goal of better characterizing IPF pathobiology using proteomic measurements 7-10. These efforts have identified individual proteins, including blood MMP-7 11,12 , CCL18 13 , and blood surfactant protein D 14,15 , as potential prognostic biomarkers. However, it has been difficult to replicate these findings across multiple cohorts 16,17 , especially when attempting to validate specific, prognostically-relevant cutoff concentrati...

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Inference of Cellular Immune Environments in Sputum and Peripheral Blood Associated with Acute Exacerbations of COPD

Abstract: Associate Editor William H. Guilford oversaw the review of this article.

Cited by 4 publications

References 57 publications

CircRNA Expression Profile in Lung Cancer Complicated with Chronic Obstructive Pulmonary Disease Patients

CircRNA Expression Profile in Lung Cancer Complicated with Chronic Obstructive Pulmonary Disease Patients

A blood and bronchoalveolar lavage protein signature of rapid FEV1 decline in smoking-associated COPD

Identification of a unique temporal signature in blood and BAL associated with IPF progression

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