Novel Insight into Ferroptosis-related Genes, Molecular Subtypes, and Immune Characteristics in Intracranial Aneurysms

Overview

Journal Inflamm Res

Specialties Allergy & Immunology
Pathology

Date 2022 Sep 4

PMID 36057911

Authors

Shifu Li

Qian Zhang

Zhou Chen

Zheng Huang

Longbo Zhang

Fenghua Chen

Affiliations

Soon will be listed here.

Abstract

Objectives: This study aimed to identify the role of ferroptosis in intracranial aneurysm (IA).

Methods: GSE122897, GSE75436, GSE15629, and GSE75434 datasets were downloaded from the Gene Expression Omnibus database. The differentially expressed ferroptosis-related genes (DEFRGs) were selected to construct a diagnostic model integrating with machine learning. Then, a consensus clustering algorithm was performed to classify IA patients into distinct ferroptosis-related clusters. Functional analyses, including GO, KEGG, GSVA, and GSEA analyses, were conducted to elucidate the underlying mechanisms. ssGSEA and xCell algorithms were performed to uncover the immune characteristics.

Results: We identified 28 DEFRGs between IAs and controls from the GSE122897 dataset. GO and KEGG results showed that these genes were enriched in cytokine activity, ferroptosis, and the IL-17 signaling pathway. Immune analysis showed that the IAs had higher levels of immune infiltration. A four FRGs model (MT3, CDKN1A, ZEP69B, and ABCC1) was established and validated with great IA diagnostic ability. We divided the IA samples into two clusters and found that cluster 2 had a higher proportion of rupture and immune infiltration. We identified 10 ferroptosis phenotypes-related markers in IAs.

Conclusion: Ferroptosis and the immune microenvironment are closely associated with IAs, providing a basis for understanding the IA development.

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