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The Combined Model of CX3CR1-Related Immune Infiltration Genes to Evaluate the Prognosis of Idiopathic Pulmonary Fibrosis
BACKGROUND: High expression of chemokine (C-X3-C motif) receptor 1 (CX3CR1) was shown to contribute to the progression of many fibrotic diseases. However, there is still no study for the role of CX3CR1 in idiopathic pulmonary fibrosis (IPF). Therefore, we aimed to identify CX3CR1-related immune infi...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866189/ https://www.ncbi.nlm.nih.gov/pubmed/35222428 http://dx.doi.org/10.3389/fimmu.2022.837188 |
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author | Cai, Haozheng Chen, Shijie Li, Xinyu Liu, Hanying Zhang, Ying Zhuang, Quan |
author_facet | Cai, Haozheng Chen, Shijie Li, Xinyu Liu, Hanying Zhang, Ying Zhuang, Quan |
author_sort | Cai, Haozheng |
collection | PubMed |
description | BACKGROUND: High expression of chemokine (C-X3-C motif) receptor 1 (CX3CR1) was shown to contribute to the progression of many fibrotic diseases. However, there is still no study for the role of CX3CR1 in idiopathic pulmonary fibrosis (IPF). Therefore, we aimed to identify CX3CR1-related immune infiltration genes (IIGs) in IPF and establish a combined risk model to evaluate the prognosis of IPF. METHODS: A discovery cohort of IPF patients (GSE70867) was downloaded from the Gene Expression Omnibus dataset. We identified the composition of 22 kinds of immune cells infiltration by CIBERSORT. The Cox regression model with the LASSO method was used for identifying prognostic genes and developing CX3CR1-related IIGs. Kaplan–Meier was applied to plot the survival curve of prognosis model. Peripheral blood mononuclear cell (PBMC) and bronchoalveolar lavage fluid (BALF) were collected to be tested by quantitative reverse transcriptase-PCR (qRT-PCR) from 15 clinical samples, including 8 healthy controls (HC), 4 patients with usual interstitial pneumonia (UIP) and 3 patients with pulmonary fibrosis (FIB). RESULTS: We found that high expression of CX3CR1 in BALF contributed to the poor prognosis in IPF patients. ALR4C, RAB37, GPR56, MARCKS, PXN and RASSF2 were identified as CX3CR1-related IIGs, which were highly expressed in PBMC of UIP/FIB patients than that of HC. Moreover, the expression of PXN was higher in FIB patients’ PBMC than that of UIP ones. In the cohort of IPF patients, high infiltration of activated NK cells in BALF caused poor survival compared to low infiltration group. The infiltration of activated NK was regulated by CX3CR1-related IIGs. The combined risk model predicted that high expression of CX3CR1-related IIGs and high infiltrated activated NK cells caused poor prognosis in IPF patients. CONCLUSION: We identified a group of CX3CR1-related IIGs in IPF patients. This combined risk model provided new insights in the prognosis and therapy of IPF. |
format | Online Article Text |
id | pubmed-8866189 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88661892022-02-25 The Combined Model of CX3CR1-Related Immune Infiltration Genes to Evaluate the Prognosis of Idiopathic Pulmonary Fibrosis Cai, Haozheng Chen, Shijie Li, Xinyu Liu, Hanying Zhang, Ying Zhuang, Quan Front Immunol Immunology BACKGROUND: High expression of chemokine (C-X3-C motif) receptor 1 (CX3CR1) was shown to contribute to the progression of many fibrotic diseases. However, there is still no study for the role of CX3CR1 in idiopathic pulmonary fibrosis (IPF). Therefore, we aimed to identify CX3CR1-related immune infiltration genes (IIGs) in IPF and establish a combined risk model to evaluate the prognosis of IPF. METHODS: A discovery cohort of IPF patients (GSE70867) was downloaded from the Gene Expression Omnibus dataset. We identified the composition of 22 kinds of immune cells infiltration by CIBERSORT. The Cox regression model with the LASSO method was used for identifying prognostic genes and developing CX3CR1-related IIGs. Kaplan–Meier was applied to plot the survival curve of prognosis model. Peripheral blood mononuclear cell (PBMC) and bronchoalveolar lavage fluid (BALF) were collected to be tested by quantitative reverse transcriptase-PCR (qRT-PCR) from 15 clinical samples, including 8 healthy controls (HC), 4 patients with usual interstitial pneumonia (UIP) and 3 patients with pulmonary fibrosis (FIB). RESULTS: We found that high expression of CX3CR1 in BALF contributed to the poor prognosis in IPF patients. ALR4C, RAB37, GPR56, MARCKS, PXN and RASSF2 were identified as CX3CR1-related IIGs, which were highly expressed in PBMC of UIP/FIB patients than that of HC. Moreover, the expression of PXN was higher in FIB patients’ PBMC than that of UIP ones. In the cohort of IPF patients, high infiltration of activated NK cells in BALF caused poor survival compared to low infiltration group. The infiltration of activated NK was regulated by CX3CR1-related IIGs. The combined risk model predicted that high expression of CX3CR1-related IIGs and high infiltrated activated NK cells caused poor prognosis in IPF patients. CONCLUSION: We identified a group of CX3CR1-related IIGs in IPF patients. This combined risk model provided new insights in the prognosis and therapy of IPF. Frontiers Media S.A. 2022-02-10 /pmc/articles/PMC8866189/ /pubmed/35222428 http://dx.doi.org/10.3389/fimmu.2022.837188 Text en Copyright © 2022 Cai, Chen, Li, Liu, Zhang and Zhuang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Cai, Haozheng Chen, Shijie Li, Xinyu Liu, Hanying Zhang, Ying Zhuang, Quan The Combined Model of CX3CR1-Related Immune Infiltration Genes to Evaluate the Prognosis of Idiopathic Pulmonary Fibrosis |
title | The Combined Model of CX3CR1-Related Immune Infiltration Genes to Evaluate the Prognosis of Idiopathic Pulmonary Fibrosis |
title_full | The Combined Model of CX3CR1-Related Immune Infiltration Genes to Evaluate the Prognosis of Idiopathic Pulmonary Fibrosis |
title_fullStr | The Combined Model of CX3CR1-Related Immune Infiltration Genes to Evaluate the Prognosis of Idiopathic Pulmonary Fibrosis |
title_full_unstemmed | The Combined Model of CX3CR1-Related Immune Infiltration Genes to Evaluate the Prognosis of Idiopathic Pulmonary Fibrosis |
title_short | The Combined Model of CX3CR1-Related Immune Infiltration Genes to Evaluate the Prognosis of Idiopathic Pulmonary Fibrosis |
title_sort | combined model of cx3cr1-related immune infiltration genes to evaluate the prognosis of idiopathic pulmonary fibrosis |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866189/ https://www.ncbi.nlm.nih.gov/pubmed/35222428 http://dx.doi.org/10.3389/fimmu.2022.837188 |
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