A ferroptosis-related gene signature for graft loss prediction following renal allograft

ABSTRACT

Allogeneic kidney transplantation (renal allograft) is the most effective treatment for advanced kidney disease. Previous studies have indicated that ferroptosis participates in the progression of acute kidney injury and renal transplant failure. However, few studies have evaluated the prognostic value of ferroptosis on renal transplantation outcomes. In this study, a total of 22 differentially expressed ferroptosis-related genes (DFGs) were identified, which were mainly enriched in infection-related pathways. Next, a ferroptosis-related gene signature, including GA-binding protein transcription factor subunit beta 1 (GABPB1), cyclin-dependent kinase inhibitor 1A (CDKN1A), Toll-like receptor 4 (TLR4), C-X-C motif chemokine ligand 2 (CXCL2), caveolin 1 (CAV1), and ribonucleotide reductase subunit M2 (RRM2), was constructed to predict graft loss following renal allograft. Moreover, receiver operating characteristic (ROC) curves (area under the ROC curve [AUC] > 0.8) demonstrated the accuracy of the gene signature and univariate Cox analysis suggested that the gene signature could play an independent role in graft loss (p < 0.05). Furthermore, the nomogram and calibration plots also indicated the good prognostic capability of the gene signature. Finally, immune-related and cytokine signaling pathways were mostly enriched in renal allograft patients with poor outcomes. Considered together, a ferroptosis-related gene signature and nomogram based on DFGs were created to predict the 1-, 2- and 3- year graft loss probability of renal allograft patients.The gene signature could serve as a valuable biomarker for predicting graft loss, contributing to improving the outcome of allogeneic kidney transplantation.

GRAPHICAL ABSTRACT

KEYWORDS:

• Ferroptosis
• renal allograft
• prognosis
• gene signature
• nomogram

Highlights

1. A ferroptosis related gene signature for predicting the graft loss after renal allograft was established

2. The gene signature could act as a an independent factor

3. The immune-related pathways and cytokine signaling pathways were mostly enriched in the high-risk group

Disclosure statement

All of the authors declared that no author has financial or other contractual agreements that might cause conflicts of interest.

Ethics approval and consent to participate

Not applicable. All data in this study are publicly available.

Data availability

The datasets (GSE21374, GSE36059, and GSE48581) included in the present study can be found in GEO database (https://www.ncbi.nlm.nih.gov/geo/).

Author contributions

Zhong Zeng conceived and designed this study, Zhenlei Fan and Tao Liu downloaded and analyzed the data, and wrote the manuscript, Hanfei Huang, Jie Lin and Zhong Zeng revised the manuscript. All authors read and approved the manuscript for publication.

Supplementary material

Supplemental data for this article can be accessed here

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [81960124 and 81760119].