https://orcid.org/0000-0002-2451-0174
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Abstract
Purpose
Immune infiltration plays a pivotal role in the pathogenesis of mucosal damage in ulcerative colitis (UC). The objective of this study was to systematically analyze and identify genetic characteristics associated with immune infiltration in UC.
Patients and Methods
Gene expression data from three independent datasets obtained from the Gene Expression Omnibus (GEO) were utilized. By employing the ssGSEA and CIBERSORT algorithms, we estimated the extent of immune cell infiltration in UC samples. Subsequently, Weighted Correlation Network Analysis (WGCNA) was performed to identify gene modules exhibiting significant associations with immune infiltration, and further identification of hub genes associated with immune infiltration was accomplished using least absolute shrinkage and selection operator (LASSO) regression analysis. The relationship between the identified hub genes and clinical information was subsequently investigated.
Results
Our findings revealed significant activation of both innate and adaptive immune cells in UC. Notably, the expression levels of CD44, IL1B, LYN, and ITGA5 displayed strong correlations with immune cell infiltration within the mucosa of UC patients. Immunohistochemical analysis confirmed the significant upregulation of CD44, LYN, and ITGA5 in UC samples, and their expression levels were found to be significantly associated with common inflammatory markers, including the systemic immune inflammation indices, C-reactive protein, and erythrocyte sedimentation rate.
Conclusion
CD44, LYN, and ITGA5 are involved in the immune infiltration pathogenesis of UC and may be potential therapeutic targets for UC.
Abbreviations
UC, ulcerative colitis; CD, Crohn’s disease; ssGSEA, single-sample gene set enrichment analysis; DEGs, Differential Expressed Genes, BP, Biological Process, CC, Cellular Component, MF, Molecular Function, LASSO, least absolute shrinkage and selection operator; IHC, immunohistochemical; IOD, integrated optical density; SII, systemic immune inflammation index.
Data Sharing Statement
The datasets had analyzed during the current study are available in the Gene Expression Omnibus (GEO). The data used in this study can be accessed at the following link: GSE92415 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE92415), GSE206285 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE206285), andGSE1687 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE16879). The data that support the findings of this study are available from the corresponding author upon reasonable request.
Ethics Approval and Consent to Participate
This study was conducted in accordance with the Declaration of Helsinki. This study was approved by ethics committee of the Renmin Hospital of Wuhan University (WDRY2021-K025). All subjects signed a document of informed consent.
Acknowledgments
Great thanks would be extended to the National Cancer Institute for providing Gene Expression Omnibus (GEO) data set. Appreciation for enhancing the paper structure and refining content, by Qingmin He and to editors and the anonymous reviewers as well for their valuable comments and suggestions concerning the quality improvement of this paper.
Author Contributions
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Disclosure
The authors have no relevant financial or non-financial interests to disclose.