S100A12 as Biomarker of Disease Severity and Prognosis in Patients With Idiopathic Pulmonary Fibrosis

BackgroundIdiopathic pulmonary fibrosis (IPF) is one of interstitial lung diseases (ILDs) with poor prognosis. S100 calcium binding protein A12 (S100A12) has been reported as a prognostic serum biomarker in the IPF, but its correlation with IPF remains unclear in the lung tissue and bronchoalveolar...

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Main Authors: Yupeng Li, Yaowu He, Shibin Chen, Qi Wang, Yi Yang, Danting Shen, Jing Ma, Zhe Wen, Shangwei Ning, Hong Chen
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-02-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2022.810338/full
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author Yupeng Li
Yaowu He
Shibin Chen
Qi Wang
Yi Yang
Danting Shen
Jing Ma
Zhe Wen
Shangwei Ning
Hong Chen
author_facet Yupeng Li
Yaowu He
Shibin Chen
Qi Wang
Yi Yang
Danting Shen
Jing Ma
Zhe Wen
Shangwei Ning
Hong Chen
author_sort Yupeng Li
collection DOAJ
description BackgroundIdiopathic pulmonary fibrosis (IPF) is one of interstitial lung diseases (ILDs) with poor prognosis. S100 calcium binding protein A12 (S100A12) has been reported as a prognostic serum biomarker in the IPF, but its correlation with IPF remains unclear in the lung tissue and bronchoalveolar lavage fluids (BALF).MethodsDatasets were collected from the Gene Expression Omnibus (GEO) database. Person correlation coefficient, Kaplan–Meier analysis, Cox regression analysis, functional enrichment analysis and so on were used. And single cell RNA-sequencing (scRNA-seq) analysis was also used to explore the role of S100A12 and related genes in the IPF.ResultsS100A12 was mainly and highly expressed in the monocytes, and its expression was downregulated in the lung of patients with IPF according to scRNA-seq and the transcriptome analysis. However, S100A12 expression was upregulated both in blood and BALF of patients with IPF. In addition, 10 genes were found to interact with S100A12 according to protein–protein interaction (PPI) network, and the first four transcription factors (TF) targeted these genes were found according to hTFtarget database. Two most significant co-expression genes of S100A12 were S100A8 and S100A9. The 3 genes were significantly negatively associated with lung function and positively associated with the St. George’s Respiratory Questionnaire (SGRQ) scores in the lung of patients with IPF. And, high expression of the 3 genes was associated with higher mortality in the BALF, and shorter transplant-free survival (TFS) and progression-free survival (PFS) time in the blood. Prognostic predictive value of S100A12 was more superior to S100A8 and S100A9 in patients with IPF, and the composited variable [S100A12 + GAP index (gender, age, and physiological index)] may be a more effective predictive index.ConclusionThese results imply that S100A12 might be an efficient disease severity and prognostic biomarker in patients with IPF.
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spelling doaj.art-15b49101912e4a7a8a50a0496bc767c32022-12-22T01:30:15ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-02-011310.3389/fimmu.2022.810338810338S100A12 as Biomarker of Disease Severity and Prognosis in Patients With Idiopathic Pulmonary FibrosisYupeng Li0Yaowu He1Shibin Chen2Qi Wang3Yi Yang4Danting Shen5Jing Ma6Zhe Wen7Shangwei Ning8Hong Chen9Department of Pulmonary and Critical Care Medicine, Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Pulmonary and Critical Care Medicine, Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaMedical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, ChinaDepartment of Pulmonary and Critical Care Medicine, Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Pulmonary and Critical Care Medicine, Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Pulmonary and Critical Care Medicine, Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Pulmonary and Critical Care Medicine, Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Pulmonary and Critical Care Medicine, Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin, ChinaDepartment of Pulmonary and Critical Care Medicine, Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaBackgroundIdiopathic pulmonary fibrosis (IPF) is one of interstitial lung diseases (ILDs) with poor prognosis. S100 calcium binding protein A12 (S100A12) has been reported as a prognostic serum biomarker in the IPF, but its correlation with IPF remains unclear in the lung tissue and bronchoalveolar lavage fluids (BALF).MethodsDatasets were collected from the Gene Expression Omnibus (GEO) database. Person correlation coefficient, Kaplan–Meier analysis, Cox regression analysis, functional enrichment analysis and so on were used. And single cell RNA-sequencing (scRNA-seq) analysis was also used to explore the role of S100A12 and related genes in the IPF.ResultsS100A12 was mainly and highly expressed in the monocytes, and its expression was downregulated in the lung of patients with IPF according to scRNA-seq and the transcriptome analysis. However, S100A12 expression was upregulated both in blood and BALF of patients with IPF. In addition, 10 genes were found to interact with S100A12 according to protein–protein interaction (PPI) network, and the first four transcription factors (TF) targeted these genes were found according to hTFtarget database. Two most significant co-expression genes of S100A12 were S100A8 and S100A9. The 3 genes were significantly negatively associated with lung function and positively associated with the St. George’s Respiratory Questionnaire (SGRQ) scores in the lung of patients with IPF. And, high expression of the 3 genes was associated with higher mortality in the BALF, and shorter transplant-free survival (TFS) and progression-free survival (PFS) time in the blood. Prognostic predictive value of S100A12 was more superior to S100A8 and S100A9 in patients with IPF, and the composited variable [S100A12 + GAP index (gender, age, and physiological index)] may be a more effective predictive index.ConclusionThese results imply that S100A12 might be an efficient disease severity and prognostic biomarker in patients with IPF.https://www.frontiersin.org/articles/10.3389/fimmu.2022.810338/fullIdiopathic pulmonary fibrosisbiomarkerS100A12prognosisinflammation
spellingShingle Yupeng Li
Yaowu He
Shibin Chen
Qi Wang
Yi Yang
Danting Shen
Jing Ma
Zhe Wen
Shangwei Ning
Hong Chen
S100A12 as Biomarker of Disease Severity and Prognosis in Patients With Idiopathic Pulmonary Fibrosis
Frontiers in Immunology
Idiopathic pulmonary fibrosis
biomarker
S100A12
prognosis
inflammation
title S100A12 as Biomarker of Disease Severity and Prognosis in Patients With Idiopathic Pulmonary Fibrosis
title_full S100A12 as Biomarker of Disease Severity and Prognosis in Patients With Idiopathic Pulmonary Fibrosis
title_fullStr S100A12 as Biomarker of Disease Severity and Prognosis in Patients With Idiopathic Pulmonary Fibrosis
title_full_unstemmed S100A12 as Biomarker of Disease Severity and Prognosis in Patients With Idiopathic Pulmonary Fibrosis
title_short S100A12 as Biomarker of Disease Severity and Prognosis in Patients With Idiopathic Pulmonary Fibrosis
title_sort s100a12 as biomarker of disease severity and prognosis in patients with idiopathic pulmonary fibrosis
topic Idiopathic pulmonary fibrosis
biomarker
S100A12
prognosis
inflammation
url https://www.frontiersin.org/articles/10.3389/fimmu.2022.810338/full
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