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Identification of Common Ferroptosis Signature Genes in Hepatocellular Carcinoma and Renal Clear Cell Carcinoma: Implications for Diagnosis and Prognosis

Xusheng Zhang1#, Hongcai Zhou1#, Peng Wei1, Weihu Ma1, Bendong Chen1,2*

Objective: To investigate the biological significance of ferroptosis in hepatocellular carcinoma and renal clear cell carcinoma based on their disease commonality.

Methods: Based on the mRNA-seq data and matched clinical data of the two cancers in the GEO (Gene Expression Omnibus) database and TCGA (The Cancer Genome Atlas) database, we used R package and part of online analysis tools to find the differentially expressed ferroptosis genes in the two cancers, and then used LASSO (Least Absolute Shrinkage and Selection Operator) regression analysis to further screen the ferroptosis signature genes in the two cancers, explored their functional characteristics and clinical significance in the two cancers based on the expression of the ferroptosis signature genes.

Results: Four ferroptosis genes, G6PD, NRAS, CDCA3 and NDRG1 were significantly upregulated in hepatocellular carcinoma and renal clear cell carcinoma showed good diagnostic efficacy for both cancers, and were significantly associated with patient survival prognosis. The risk model based on the four characteristic genes showed good predictive efficacy and has potential clinical application, upregulation of NRAS expression may contribute to the pathogenesis and progression of cancer through activation of MAPK/ERK signalling pathway.

Conclusion: G6PD, NRAS, CDCA3, and NDRG1 are common ferroptosis signature genes for hepatocellular carcinoma and renal clear cell carcinoma, which have good diagnostic and prognostic predictive efficacy for both cancers, upregulation of NRAS expression may contribute to the pathogenesis and progression of two cancer through activation of MAPK/ERK signaling pathway.

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