Identification of key modules and hub genes associated with lung function in idiopathic pulmonary fibrosis

Background Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease, characterized by a decline in lung function. To date, the pathophysiologic mechanisms associated with lung dysfunction remain unclear, and no effective therapy has been identified to improve lung function. Methods In the present study, we used weighted gene co-expression network analysis (WGCNA) to identify key modules and hub genes associated with lung function in IPF. Three datasets, containing clinical information, were downloaded from Gene Expression Omnibus. WGCNA was performed on the GSE32537 dataset. Differentially expressed gene s (DEGs) between IPF patients and healthy controls were also identified to filter hub genes. The relationship between hub genes and lung function was then validated using the GSE47460 and GSE24206 datasets. Results The red module, containing 267 genes, was positively correlated with the St. George’s Respiratory Questionnaire score (r = 0.37, p < 0.001) and negatively correlated with the percent predicted forced vital capacity (FVC% predicted) (r = − 0.46, p < 0.001) and the percent predicted diffusion capacity of the lung for carbon monoxide (Dlco% predicted) (r = − 0.42, p < 0.001). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis suggested that the genes in the red module were primarily involved in inflammation and immune pathways. Based on Module Membership and Gene Significance, 32 candidate hub genes were selected in the red module to construct a protein-protein interaction network . Based on the identified DEGs and the degree of connectivity in the network, we identified three hub genes, including interleukin 6 (IL6), suppressor of cytokine signaling-3 (SOCS3), and serpin family E member 1 (SERPINE1). In the GSE47460 dataset, Spearman correlation coefficients between Dlco% predicted and expression levels of IL6, SERPINE1, SOCS3 were –0.32, –0.41, and –0.46, respectively. Spearman correlation coefficients between FVC% predicted and expression levels of IL6, SERPINE1, SOCS3 were –0.29, –0.33, and –0.27, respectively. In the GSE24206 dataset, all three hub genes were upregulated in patients with advanced IPF. Conclusion We identified three hub genes that negatively correlated with the lung function of IPF patients. Our results provide insights into the pathogenesis underlying the progressive disruption of lung function, and the identified hub genes may serve as biomarkers and potential therapeutictargets for the treatment of IPF patients.

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Home spirometry in patients with idiopathic pulmonary fibrosis: data from the INMARK trial

European Respiratory Journal ◽

10.1183/13993003.01518-2020 ◽

2021 ◽

pp. 2001518

Author(s):

Imre Noth ◽

Vincent Cottin ◽

Nazia Chaudhuri ◽

Tamera J Corte ◽

Kerri A Johannson ◽

...

Keyword(s):

Lung Function ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Pearson Correlation ◽

Correlation Coefficients ◽

Strong Correlations ◽

Lung Function Decline ◽

Open Label ◽

Rates Of Change ◽

Rate Of Decline

Data from the INMARK trial were used to investigate the feasibility and validity of home spirometry as a measure of lung function decline in patients with idiopathic pulmonary fibrosis (IPF).Subjects with IPF and preserved forced vital capacity (FVC) were randomised to receive nintedanib or placebo for 12 weeks followed by open-label nintedanib for 40 weeks. Clinic spirometry was conducted at baseline and weeks 4, 8, 12, 16, 20, 24, 36 and 52. Subjects were asked to perform home spirometry at least once a week and ideally daily. Correlations between home- and clinic-measured FVC and rates of change in FVC were assessed using Pearson correlation coefficients.In total, 346 subjects were treated. Mean adherence to weekly home spirometry decreased over time but remained above 75% in every 4-week period. Over 52 weeks, mean adherence was 86%. Variability in change from baseline in FVC was greater when measured by home rather than clinic spirometry. Strong correlations were observed between home- and clinic-measured FVC at all time-points (r=0.72 to 0.84), but correlations between home- and clinic-measured rates of change in FVC were weak (r=0.26 for rate of decline in FVC over 52 weeks).Home spirometry was a feasible and valid measure of lung function in patients with IPF and preserved FVC, but estimates of the rate of FVC decline obtained using home spirometry were poorly correlated with those based on clinic spirometry.

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A Ferroptosis-Related Gene Signature for Lung Function and Quality of Life in Patients with Idiopathic Pulmonary Fibrosis

10.21203/rs.3.rs-201670/v1 ◽

2021 ◽

Author(s):

Yupeng Li ◽

Shangwei Ning ◽

Yi Yang ◽

Hong Chen ◽

Chen Wang

Keyword(s):

Quality Of Life ◽

Lung Function ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Mirna Target ◽

Integrin Subunit ◽

Ppi Network ◽

Lung Dysfunction ◽

Key Genes

Abstract Background: Rapid advances in genetic and genomic technologies have begun to reshape our understanding of idiopathic pulmonary fibrosis (IPF). Ferroptosis, an iron-dependent form of regulated cell death, play an important role in the development of IPF. Therefore, our study aimed to explore the role of ferroptosis-related genes (FRGs) and their correlation with lung dysfunction and quality of life in patients with IPF. Methods: Datasets were acquired by researching the Gene Expression Omnibus. FRGs were acquired by researching GeneCard database and PubMed. Ferroptosis-related differentially expressed genes (FRDEGs) were identified according to integrating FRGs and the DEGs identified in the GSE110147 dataset. Candidate key genes were identified from the miRNA-target FRDEGs network and protein-protein interactions (PPI) network. The relationship between key genes and lung function or quality of life was calculated using the GSE32537 datasets.Results: 293 FRGs were obtained, and 71 FRDEGs were identified. According to enrichment analysis, cell growth and death and pathways associated cancer were the important pathways, and significant biological processes were mainly consisted of cellular responses to stimulus and various situations. In addition, this study constructed an PPI network and a miRNA-target network based on the 71 FRDEGs, determined 19 candidate key genes. Furthermore, acyl-CoA synthetase long chain family member 1 (ACSL1), integrin subunit beta 8 (ITGB8) and ceruloplasmin (CP) were identified as the key genes. The expression level of ACSL1 was the strongest predictor for lung function (negatively) including percent predicted forced vital capacity (FVC% predicted) and percent predicted diffusion capacity of the lung for carbon monoxide (Dlco% predicted) and quality of life (negatively). In addition, ITGB8 and CP were negatively associated with FVC% predicted. According to DrugBank and PubMed, 4 drugs and 16 drugs have been found to act on ACSL1 and CP, respectively. Conclusion: These results imply that FRGs may shed new understanding on disease mechanism and provide potential biomarkers and therapy target to predict IPF progression.

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A ferroptosis-related gene signature for lung function and quality of life in patients with idiopathic pulmonary fibrosis

10.21203/rs.3.rs-201670/v2 ◽

2021 ◽

Author(s):

Yupeng Li ◽

Shangwei Ning ◽

Yi Yang ◽

Hong Chen ◽

Chen Wang ◽

...

Keyword(s):

Quality Of Life ◽

Lung Function ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Mirna Target ◽

Integrin Subunit ◽

Ppi Network ◽

Lung Dysfunction ◽

Key Genes

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Identification of Hub Genes and Pathways Associated With Idiopathic Pulmonary Fibrosis via Bioinformatics Analysis

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.711239 ◽

2021 ◽

Vol 8 ◽

Author(s):

Hanxi Wan ◽

Xinwei Huang ◽

Peilin Cong ◽

Mengfan He ◽

Aiwen Chen ◽

...

Keyword(s):

Gene Expression ◽

Network Analysis ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Enrichment Analysis ◽

Gene Expression Omnibus ◽

Ppi Network ◽

Hub Genes ◽

Expression Levels ◽

Protein Protein Interaction

Idiopathic pulmonary fibrosis (IPF) is a progressive disease whose etiology remains unknown. The purpose of this study was to explore hub genes and pathways related to IPF development and prognosis. Multiple gene expression datasets were downloaded from the Gene Expression Omnibus database. Weighted correlation network analysis (WGCNA) was performed and differentially expressed genes (DEGs) identified to investigate Hub modules and genes correlated with IPF. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and protein-protein interaction (PPI) network analysis were performed on selected key genes. In the PPI network and cytoHubba plugin, 11 hub genes were identified, including ASPN, CDH2, COL1A1, COL1A2, COL3A1, COL14A1, CTSK, MMP1, MMP7, POSTN, and SPP1. Correlation between hub genes was displayed and validated. Expression levels of hub genes were verified using quantitative real-time PCR (qRT-PCR). Dysregulated expression of these genes and their crosstalk might impact the development of IPF through modulating IPF-related biological processes and signaling pathways. Among these genes, expression levels of COL1A1, COL3A1, CTSK, MMP1, MMP7, POSTN, and SPP1 were positively correlated with IPF prognosis. The present study provides further insights into individualized treatment and prognosis for IPF.

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Effect of baseline FVC on decline in lung function with nintedanib in patients with idiopathic pulmonary fibrosis (IPF): results from the INPULSIS® trials

Pneumologie ◽

10.1055/s-0036-1572000 ◽

2016 ◽

Vol 70 (S 01) ◽

Author(s):

M Pfeifer ◽

M Kolb ◽

T Kimura ◽

S Stowasser ◽

C Hallmann ◽

...

Keyword(s):

Lung Function ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis

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Analysis of patients with Idiopathic Pulmonary Fibrosis (IPF) with more severe lung function impairment treated with pirfenidone in RECAP

Pneumologie ◽

10.1055/s-0037-1619244 ◽

2018 ◽

Vol 72 (S 01) ◽

pp. S47-S48

Author(s):

U Costabel ◽

C Albera ◽

KU Kirchgaessler ◽

F Gilberg ◽

U Petzinger ◽

...

Keyword(s):

Lung Function ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Function Impairment ◽

Lung Function Impairment ◽

Severe Lung

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Chemotherapy in idiopathic pulmonary fibrosis and small-cell lung cancer with poor lung function

BMC Pulmonary Medicine ◽

10.1186/s12890-021-01489-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xiyue Zhang ◽

Wei Li ◽

Chunyan Li ◽

Jie Zhang ◽

Zhenzhong Su

Keyword(s):

Lung Cancer ◽

Lung Function ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung ◽

High Resolution Computed Tomography ◽

Chemotherapeutic Regimen

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with unclear pathogenesis. IPF is considered as a risk factor for lung cancer. Compared to other lung cancers, small-cell lung cancer (SCLC) has a lower incidence, but has a more aggressive course. Patients with IPF and SCLC have a lower survival rate, more difficult treatment, and poorer prognosis. Case presentation Case 1 was of a 66-year-old man with IPF for 5 years, who was admitted to our hospital for dyspnea. Case 2 was of a 68-year-old woman, who presented with chest pains, cough, and dyspnea. Both patients had extremely poor lung function. High-resolution computed tomography and pathology revealed that both patients had IPF and SCLC. Chemotherapy comprising nedaplatin (80 mg/m2) and etoposide (100 mg for 5 days) was initiated for both patients. Antifibrotic agents were continued during the chemotherapeutic regimen. Both patients showed improvement in their condition after treatment. Conclusion The favorable outcomes in these 2 cases suggests that chemotherapy is worth considering in the management of patients having SCLC and IPF with poor lung function.

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Impact of Lung Biopsy on Lung Function in Idiopathic Pulmonary Fibrosis

Respiration ◽

10.1159/000509557 ◽

2020 ◽

pp. 1-8

Author(s):

Pierre-Henri Aussedat ◽

Nader Chebib ◽

Kais Ahmad ◽

Jean-Charles Glerant ◽

Gabrielle Drevet ◽

...

Keyword(s):

Lung Function ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Forced Vital Capacity ◽

Lung Biopsy ◽

Vital Capacity ◽

Forced Expiratory Volume ◽

Surgical Lung Biopsy ◽

Before And After ◽

The Impact

Background: Video-assisted surgical lung biopsy (SLB) is performed in 10–30% of cases to establish the diagnosis of idiopathic pulmonary fibrosis (IPF). Objectives: The aim of the study was to analyze the impact of SLB on lung function in patients eventually diagnosed with IPF. Methods: This is an observational, retrospective, monocentric study of all consecutive patients eventually diagnosed with IPF in multidisciplinary discussion who underwent SLB over 10 years in a specialized center. The primary end point was the variation in forced vital capacity (FVC) before and after the SLB. The secondary end points were the variations in forced expiratory volume in one second (FEV1), total lung capacity (TLC), carbon monoxide diffusion capacity (DLCO), and morbidity and mortality associated with the SLB. Results: In 118 patients who underwent SLB and were diagnosed with IPF, a relative decrease in FVC of 4.8% (p < 0.001) was found between measurements performed before and after the procedure. The mean FVC decrease was 156 ± 386 mL in an average period of 185 days, representing an annualized decline of 363 ± 764 mL/year. A significant decrease was also observed after SLB in FEV1, TLC, and DLCO. Complications within 30 days of SLB occurred in 14.4% of patients. Two patients (1.7%) died within 30 days, where one of them had poor lung function. Survival at 1 year was significantly poorer in patients with FVC <50% at baseline. Conclusion: In this uncontrolled study in patients ultimately diagnosed with IPF, SLB was followed by a significant decline in FVC, which appears to be numerically greater than the average decline in the absence of treatment in the literature. Summary at a Glance: This study evaluated the change in lung function in 118 consecutive patients diagnosed with idiopathic pulmonary fibrosis by surgical lung biopsy. Forced vital capacity decreased by 156 ± 386 mL in a mean of 185 days between the last measurement before and first measurement after biopsy, representing an annualized decline of 363 ± 764 mL/year.

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