Identification of new hub- ferroptosis-related genes in Lupus Nephritis

Abstract

Background: Lupus Nephritis (LN) is the primary causation of kidney injury in systemic lupus erythematosus (SLE). Ferroptosis is a programmed cell death. Therefore, understanding the crosstalk between LN and ferroptosis is still a significant challenge. Methods: We obtained the expression profile of LN kidney biopsy samples from the Gene Expression Omnibus database and utilised the R-project software to identify differentially expressed genes (DEGs). Then, we conducted a functional correlation analysis. Ferroptosis-related genes (FRGs) and differentially expressed genes (DEGs) crossover to select FRGs with LN. Afterwards, we used CIBERSORT to assess the infiltration of immune cells in both LN tissues and healthy control samples. Finally, we performed immunohistochemistry on LN human renal tissue. Results: 10619 DEGs screened from the LN biopsy tissue were identified. 22 hub-ferroptosis-related genes with LN (FRGs-LN) were screened out. The CIBERSORT findings revealed that there were significant statistical differences in immune cells between healthy control samples and LN tissues. Immunohistochemistry further demonstrated a significant difference in HRAS, TFRC, ATM, and SRC expression in renal tissue between normal and control groups. Conclusion: We developed a signature that allowed us to identify 22 new biomarkers associated with FRGs-LN. These findings suggest new insights into the pathology and therapeutic potential of LN ferroptosis inhibitors and iron chelators.

Keywords:

• hub-ferroptosis-related genes
• ferroptosis
• lupus nephritis
• systemic lupus erythematosus
• machine learning

Disclosure statement

The authors confirm that the study was conducted independently, without any commercial or financial relationships.

Author contributions

X.-J.Z. performed software operations and wrote the manuscript. Y.C. participated in statistical analysis. L.Y. and X.-L.L. provided clinical data of L.N. D.S. and Y.-Q.L. participated in research design and revised the manuscript.

Ethics approval and consent to participate

This study was approved by the Ethics Committee in The First Affiliated Hospital of China Medical University (approve number: 2022-306-2), and the patients involved signed the informed consent form.

Data availability statement

We can acquire the data from GEO Database (GSE32591, GSE127797, GSE69438, GSE99967, GSE113342 and GSE200306) and FerrDb database.

Additional information

Funding

This work was supported by National Natural Science Foundation of China (grant no. 81273297), Shenyang Science and Technology Plan. Public Health R&D Special Project [21-173-9-67].