Building a prognostic model for clear cell renal cell carcinoma based on mitochondrial-and ferrop-tosis-related genes and exploring the mechanism of ACADSB
Objective To construct a prognostic model for clear cell renal cell carcinoma(ccRCC)based on mitochondria-and ferroptosis-related genes,and explore the value of ACADSB,a gene associated with mitochondria and ferroptosis,in ccRCC prognosis.Methods Utilizing RNA-seq and clinical data from the TCGA database,differentially expressed mitochondria-and ferroptosis-related genes between ccRCC and normal tissues were identified using the Wilcoxon test.Through univariate Cox analysis,least absolute value convergence and selection operator(LASSO)analysis and multivariate Cox analysis,genes significantly associated with survival were selected to construct the prognostic model.The prognostic model's predictive ability in ccRCC was assessed.Additionally,the expression level,prognostic predic-tion,and biological function of the core gene ACADSB were analyzed.Overexpression of ACADSB in ccRCC cell lines was conducted to investigate its impact on cell proliferation and migration in vitro.Results A prognostic model(MFrisk)was constructed based on four mitochondria-and ferroptosis-related genes(GOT1,BID,ACADSB,and PLA2G6).Patients in the high-risk group exhibited significantly shorter o-verall survival than the low-risk group(P＜0.01 for all comparisons).The model demonstrated strong pre-dictive performance for 1-year,3-year,and 5-year survival rates with area under the receiver operating characteristic(ROC)curve(AUC)of 0.733,0.771,0.783 in the training set,and 0.677,0.607,0.676 in the testing set.Univariate and multivariate Cox analyses(P＜0.01 for all comparisons)revealed that the MFrisk score was independently associated with prognosis.Additionally,overexpression of ACADSB was found to inhibit ccRCC cell proliferation and migration in vitro through cell counting kit-8(CCK-8)assay,colony formation assay,and wound-healing assay.Conclusion A prognostic model based on mitochondria-and ferroptosis-related genes(GOT1,BID,ACADSB,PLA2G6)can independently predict ccRCC prognosis.Overexpression of the key gene ACADSB leads to decreased cell proliferation and migration in ccRCC,providing insights for ccRCC treatment strategies.
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