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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2023

Open Access 01-12-2023 | Chronic Inflammatory Bowel Disease | Research

Identification of FCN1 as a novel macrophage infiltration-associated biomarker for diagnosis of pediatric inflammatory bowel diseases

Authors: Xixi Chen, Yuanqi Gao, Jinfang Xie, Huiying Hua, Chun Pan, Jiebin Huang, Mengxia Jing, Xuehua Chen, Chundi Xu, Yujing Gao, Pu Li

Published in: Journal of Translational Medicine | Issue 1/2023

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Abstract

Background

The incidence of pediatric inflammatory bowel disease (PIBD) has been steadily increasing globally. Delayed diagnosis of PIBD increases the risk of complications and contributes to growth retardation. To improve long-term outcomes, there is a pressing need to identify novel markers for early diagnosis of PIBD.

Methods

The candidate biomarkers for PIBD were identified from the GSE117993 dataset by two machine learning algorithms, namely LASSO and mSVM-RFE, and externally validated in the GSE126124 dataset and our PIBD cohort. The role of ficolin-1 (FCN1) in PIBD and its association with macrophage infiltration was investigated using the CIBERSORT method and enrichment analysis of the single-cell dataset GSE121380, and further validated using immunoblotting, qRT-PCR, and immunostaining in colon biopsies from PIBD patients, a juvenile murine DSS-induced colitis model, and THP-1-derived macrophages.

Results

FCN1 showed great diagnostic performance for PIBD in an independent clinical cohort with the AUC of 0.986. FCN1 expression was upregulated in both colorectal biopsies and blood samples from PIBD patients. Functionally, FCN1 was associated with immune-related processes in the colonic mucosa of PIBD patients, and correlated with increased proinflammatory M1 macrophage infiltration. Furthermore, single-cell transcriptome analysis and immunostaining revealed that FCN1 was almost exclusively expressed in macrophages infiltrating the colonic mucosa of PIBD patients, and these FCN1+ macrophages were related to hyper-inflammation. Notably, proinflammatory M1 macrophages derived from THP-1 expressed high levels of FCN1 and IL-1β, and FCN1 overexpression in THP-1-derived macrophages strongly promoted LPS-induced activation of the proinflammatory cytokine IL-1β via the NLRP3-caspase-1 axis.

Conclusions

FCN1 is a novel and promising diagnostic biomarker for PIBD. FCN1+ macrophages enriched in the colonic mucosa of PIBD exhibit proinflammatory phenotypes, and FCN1 promotes IL-1β maturation in macrophages via the NLRP3-caspase-1 axis.
Appendix
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Metadata
Title
Identification of FCN1 as a novel macrophage infiltration-associated biomarker for diagnosis of pediatric inflammatory bowel diseases
Authors
Xixi Chen
Yuanqi Gao
Jinfang Xie
Huiying Hua
Chun Pan
Jiebin Huang
Mengxia Jing
Xuehua Chen
Chundi Xu
Yujing Gao
Pu Li
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2023
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-023-04038-1

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