Identification and validation of hub genes expressed in ulcerative colitis with metabolic dysfunction-associated steatotic liver disease

Yupei Liu; Jiao Li; Shan Tian; Qingzhi Lan; Zhiyi Sun; Chuan Liu; Weiguo Dong

doi:10.3389/fimmu.2024.1357632

Identification and validation of hub genes expressed in ulcerative colitis with metabolic dysfunction-associated steatotic liver disease

Front Immunol. 2024 Mar 14:15:1357632. doi: 10.3389/fimmu.2024.1357632. eCollection 2024.

Authors

Yupei Liu^#¹, Jiao Li^#¹, Shan Tian^#², Qingzhi Lan³, Zhiyi Sun⁴, Chuan Liu¹, Weiguo Dong¹

Affiliations

¹ Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China.
² Department of Infection, Union Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
³ Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, China.
⁴ Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, United States.

^# Contributed equally.

Abstract

Objective: Ulcerative colitis (UC) and metabolic dysfunction-associated steatotic liver disease (MASLD) are closely intertwined; however, the precise molecular mechanisms governing their coexistence remain unclear.

Methods: We obtained UC (GSE75214) and MASLD (GSE151158) datasets from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were acquired by the 'edgeR' and 'limma' packages of R. We then performed functional enrichment analysis of common DEGs. Hub genes were selected using the cytoHubba plugin and validated using GSE87466 for UC and GSE33814 for MASLD. Immunohistochemistry was employed to validate the hub genes' expression in clinical samples. Immune infiltration and gene set enrichment analyses of the hub genes were performed. Finally, we estimated the Spearman's correlation coefficients for the clinical correlation of the core genes.

Results: Within a cohort of 26 differentially regulated genes in both UC and MASLD, pathways involving cytokine-mediated signaling, cell chemotaxis, and leukocyte migration were enriched. After further validation, CXCR4, THY1, CCL20, and CD2 were identified as the hub genes. Analysis of immune infiltration patterns highlighted an association between elevated pivotal gene expression and M1 macrophage activation. Immunohistochemical staining revealed widespread expression of pivotal genes in UC- and MASLD-affected tissues. Furthermore, significant correlations were observed between the increased expression of hub genes and biochemical markers, such as albumin and prothrombin time.

Conclusion: This bioinformatics analysis highlights CXCR4, THY1, CCL20, and CD2 as crucial genes involved in the co-occurrence of UC and MASLD, providing insights into the underlying mechanisms of these two conditions.

Keywords: M1 macrophages; bioinformatics; immune; metabolic dysfunction-associated steatotic liver disease; ulcerative colitis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Albumins
Cell Movement
Colitis, Ulcerative* / genetics
Fatty Liver*
Humans
Metabolic Diseases*

Substances

Albumins

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (82170549).