Identification and verification of ferroptosis-related genes in gastric intestinal metaplasia

Biao Song; Tingting Li; Yi Zhang; Qi Yang; Bei Pei; Yun Liu; Jieyu Wang; Gang Dong; Qin Sun; Shanshan Fan; Xuejun Li

doi:10.3389/fgene.2023.1152414

Identification and verification of ferroptosis-related genes in gastric intestinal metaplasia

Front Genet. 2023 Apr 18:14:1152414. doi: 10.3389/fgene.2023.1152414. eCollection 2023.

Authors

Biao Song¹, Tingting Li², Yi Zhang¹, Qi Yang², Bei Pei¹, Yun Liu², Jieyu Wang¹, Gang Dong¹, Qin Sun², Shanshan Fan³, Xuejun Li²

Affiliations

¹ The Graduated School, Anhui University of Traditional Chinese Medicine, Hefei, China.
² Department of Gastroenterology, The Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, China.
³ Ningbo University of Technology, Ningbo, China.

Abstract

Background: Gastric intestinal metaplasia (IM) is the key link of gastric precancerous lesions. Ferroptosis is a novel form of programmed cell death. However, its impact on IM is unclear. The focus of this study is to identify and verify ferroptosis-related genes (FRGs) that may be involved in IM by bioinformatics analysis. Materials and methods: Differentially expressed genes (DEGs) were obtained from microarray dataset GSE60427 and GSE78523 downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed ferroptosis-related genes (DEFRGs) were obtained from overlapping genes of DEGs and FRGs got from FerrDb. DAVID database was used for functional enrichment analysis. Protein-protein interaction (PPI) analysis and Cytoscape software were used to screen hub gene. In addition, we built a receiver operating characteristic (ROC) curve and verified the relative mRNA expression by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Finally, the CIBERSORT algorithm was used to analyze the immune infiltration in IM. Results: First, a total of 17 DEFRGs were identified. Second, a gene module identified by Cytoscape software was considered as hub gene: PTGS2, HMOX1, IFNG, and NOS2. Third, ROC analysis showed that HMOX1 and NOS2 had good diagnostic characteristics. qRT-PCR experiments confirmed the differential expression of HMOX1 in IM and normal gastric tissues. Finally, immunoassay showed that the proportion of T cells regulatory (Tregs) and macrophages M0 in IM was relatively higher, while the proportion of T cells CD4 memory activated and dendritic cells activated was lower. Conclusion: We found significant associations between FRGs and IM, and HMOX1 may be diagnostic biomarkers and therapeutic targets for IM. These results may enhance our understanding of IM and may contribute to its treatment.

Keywords: bioinformatics; diagnosis; ferroptosis; immune landscape; intestinal metaplasia.

Grants and funding

This study was supported by the Natural Science Foundation of Anhui Province (No. 2008085MH265) and the Chinese and Western Medicine Cooperation Project for Difficult and Complicated Diseases of Anhui Province: Synergistic Treatment of Chronic Atrophic Gastritis with Intestinal Metaplasia Based on Chinese and Western Medicine (No. 0708–2021) and the Anhui Provincial Key Research and Development Program (2022e07020023).