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Identification of the ferroptosis‐related gene signature and the associated regulation axis in lung cancer and rheumatoid arthritis

Genes & Immunity (2024)Cite this article

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Abstracts

Patients with Rheumatoid arthritis (RA) have an elevated risk of lung cancer compared to the healthy population. However, there are few studies on the relationship between RA and lung adenocarcinoma (LUAD), especially the mechanisms at the genetic level. In this study, we investigated the link between RA and LUAD regarding Ferroptosis-Related Genes. The RNA-seq data of RA (GSE77298 and GSE 82107) and LUAD(GSE75037) in the Gene Expression Omnibus (GEO) database were obtained. 259 ferroptosis-related genes were obtained from the website (http://www.zhounan.org/ferrdb/).The differential genes obtained from the RA and LUAD datasets were intersected with ferroptosis-related genes to obtain the ferroptosis-related differentially expressed genes (FRDEGs). Next, the mRNA-miRNA network was constructed, then Gene Set Enrichment Analysis (GSEA) for target genes were performed. The CIBERSORT algorithm was used to analyze the immune infiltration. Finally, the results were validated using external datasets (GSE89408 and GSE48780) and The Cancer Genome Atlas (TCGA) dataset. We obtained FRDEGs common to LUAD and RA: FANCD2, HELLS, RRM2, G6PD, VLDLR. These five genes play important roles in the progression of RA and LUAD. They also hold great diagnostic value for both diseases. Also, we found that LUAD and RA share common signaling pathways and similar immune mechanisms.

Highlights

  • We identified ferroptosis-related differentially expressed genes and possible signaling pathways in LUAD and RA from a bioinformatics approach.

  • We use a bioinformatics approach to initially articulate the link between LUAD and RA.

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Fig. 1: Normalized expression matrices and PCA.
Fig. 2: Screening for FRDEGs in RA and LUAD.
Fig. 3: Correlation analysis of FRDEGs.
Fig. 4: Common pathways of LUAD and RA.
Fig. 5: Immune infiltration analysis.
Fig. 6: Validation FRDEGs in LUAD and RA.
Fig. 7: The significance of FRDEGs in clinical practice.

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Data availability

The data generated and/or analyzed during the current study are available from the corresponding author on reasonable request. Applicable on requested.

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Acknowledgements

We thank the authors of the GSE82107, GSE89408, GSE77298, GSE48780 and GSE75037 datasets for their contribution.

Funding

This work was mainly supported by grants from the National Natural Science Foundation of China (82173507, 82074160), Natural Science Foundation of Guangdong Province (2022A1515012511, 2024A1515012856), Guangdong Province Key Laboratory of Immune Regulation and Immunotherapy (2022B1212010009), the Program of National Innovation and Entrepreneurship training for college students (202212121042 and 202312121047).

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Authors and Affiliations

  1. Department of Rheumatology and Clinical Immunology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong province, China

    Bo Cai, Dandan Liu, Nuoshi Chen, Ligang Jie & Hongyan Du

  2. First College of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong province, China

    Yibin Huang

  3. School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong province, China

    Yizheng You & Hongyan Du

  4. Guangdong Province Key Laboratory of Immune Regulation and Immunotherapy, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong province, China

    Yizheng You & Hongyan Du

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Contributions

Bo Cai, and Ligang Jie designed and conducted the whole research. Yibin Huang and Dandan Liu collected the public datasets. Yizheng You,and Nuoshi Chen carried out initial data analysis. Bo Cai, Hongyan Du and Yibin Huang completed the data analysis and drafted the manuscript. Hongyan Du revised and finalized the manuscript. All authors read and approved the final paper.

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Correspondence to Ligang Jie or Hongyan Du.

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Cai, B., Huang, Y., Liu, D. et al. Identification of the ferroptosis‐related gene signature and the associated regulation axis in lung cancer and rheumatoid arthritis. Genes Immun (2024). https://doi.org/10.1038/s41435-024-00287-2

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