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已发表论文
NCF2 作为溃疡性结肠炎的新型诊断生物标志物：通过多组学分析将巨噬细胞浸润与免疫失调相联系
Authors Zhang F, Zhu J, Liu H, Ye J, Li Y, Wang B
Received 9 July 2025
Accepted for publication 25 November 2025
Published 3 December 2025 Volume 2025:18 Pages 16871—16890
DOI https://doi.org/10.2147/JIR.S552678
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Alberto Caminero
Fang Zhang,1,2,* Jianwei Zhu,3,* Haiyan Liu,4,* Jianlan Ye,1 Yuanyuan Li,5 Bingcheng Wang1
1Department of Outpatient, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China; 2Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, People’s Republic of China; 3Department of Gastroenterology Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 4Department of Rehabilitation medicine, Eastern Theater Command Air Force Hospital, Nanjing, People’s Republic of China; 5Department of Pharmacy, Eastern Theater Command Air Force Hospital, Nanjing, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Bingcheng Wang; Yuanyuan Li, Email 15063102@163.com; liyy@outlook.com
Background: Ulcerative colitis (UC) is a debilitating inflammatory condition with growing global prevalence. While immune dysregulation is a known hallmark, the specific molecular drivers and their link to fibrosis remain incompletely characterized. To address this, we conducted a study combining bioinformatic analyses of public datasets with experimental validation to identify and validate key biomarker candidates involved in UC pathogenesis.
Methods: Three publicly available ulcerative colitis gene expression datasets (GSE38713, GSE87466, GSE119600) were retrieved from the Gene Expression Omnibus (GEO). Immune cell infiltration was evaluated using ssGSEA, with significant cell types identified by Wilcoxon test and LASSO regression. DEGs were screened and analyzed using GO, KEGG, and PPI networks. Hub genes were identified using cytoHubba and validated via ROC curves. RT-qPCR, WB, and IHC validated findings in UC rat models and clinical samples.
Results: The differentially expressed genes (DEGs) were evaluated using ten distinct algorithms, resulting in the identification of eight common DEGs following an intersection analysis. 4 hub genes were further identified through validation using the GSE119600 dataset, namely Cluster of Differentiation 274 (CD274), Matrix Metallopeptidase 1 (MMP1), neutrophil cytosolic factor 2 (NCF2), Plasminogen Activator Urokinase (PLAU). Notably, NCF2 demonstrated the highest specificity and sensitivity for diagnosing ulcerative colitis (UC), suggesting its potential utility as a diagnostic biomarker. Additionally, a distinct immune cell type exhibited significant differences between UC patients and healthy controls (HC). Correlation analyses utilizing bioinformatics techniques revealed that the hub genes CD274, MMP1, NCF2, and PLAU were positively associated with macrophage infiltration, highlighting their potential role in the immune response in UC.
Conclusion: CD274, MMP1, NCF2, PLAU can serve as hub genes associated with UC. Among these, NCF2 stands out as a particularly promising target for further research into the underlying mechanisms of UC. Additionally, NCF2 may play a role in the development and progression of UC by modulating macrophage infiltration.
Keywords: ulcerative colitis, differentially expressed genes, ssGSEA, immune cells, biomarker
1Department of Outpatient, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China; 2Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, People’s Republic of China; 3Department of Gastroenterology Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 4Department of Rehabilitation medicine, Eastern Theater Command Air Force Hospital, Nanjing, People’s Republic of China; 5Department of Pharmacy, Eastern Theater Command Air Force Hospital, Nanjing, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Bingcheng Wang; Yuanyuan Li, Email 15063102@163.com; liyy@outlook.com
Background: Ulcerative colitis (UC) is a debilitating inflammatory condition with growing global prevalence. While immune dysregulation is a known hallmark, the specific molecular drivers and their link to fibrosis remain incompletely characterized. To address this, we conducted a study combining bioinformatic analyses of public datasets with experimental validation to identify and validate key biomarker candidates involved in UC pathogenesis.
Methods: Three publicly available ulcerative colitis gene expression datasets (GSE38713, GSE87466, GSE119600) were retrieved from the Gene Expression Omnibus (GEO). Immune cell infiltration was evaluated using ssGSEA, with significant cell types identified by Wilcoxon test and LASSO regression. DEGs were screened and analyzed using GO, KEGG, and PPI networks. Hub genes were identified using cytoHubba and validated via ROC curves. RT-qPCR, WB, and IHC validated findings in UC rat models and clinical samples.
Results: The differentially expressed genes (DEGs) were evaluated using ten distinct algorithms, resulting in the identification of eight common DEGs following an intersection analysis. 4 hub genes were further identified through validation using the GSE119600 dataset, namely Cluster of Differentiation 274 (CD274), Matrix Metallopeptidase 1 (MMP1), neutrophil cytosolic factor 2 (NCF2), Plasminogen Activator Urokinase (PLAU). Notably, NCF2 demonstrated the highest specificity and sensitivity for diagnosing ulcerative colitis (UC), suggesting its potential utility as a diagnostic biomarker. Additionally, a distinct immune cell type exhibited significant differences between UC patients and healthy controls (HC). Correlation analyses utilizing bioinformatics techniques revealed that the hub genes CD274, MMP1, NCF2, and PLAU were positively associated with macrophage infiltration, highlighting their potential role in the immune response in UC.
Conclusion: CD274, MMP1, NCF2, PLAU can serve as hub genes associated with UC. Among these, NCF2 stands out as a particularly promising target for further research into the underlying mechanisms of UC. Additionally, NCF2 may play a role in the development and progression of UC by modulating macrophage infiltration.
Keywords: ulcerative colitis, differentially expressed genes, ssGSEA, immune cells, biomarker