Ferroptosis-related Gene FDFT1 As A Potential Biomarker In Renal Clear Cell Carcinoma

Background and Purpose:Renal cell carcinoma is a common malignant tumor in human urinary system,and its incidence is second only to prostate cancer and bladder cancer.In recent years,the incidence of renal cell carcinoma is gradually increasing,which brings a great threat to people’s life and health.According to pathological classification,renal clear cell carcinoma is the most important histological subtype in renal cell carcinoma.At present,the treatment of renal cell carcinoma mainly depends on surgical resection,although the rapid development of molecular immunotherapy and targeted therapy for patients with advanced renal cell carcinoma has brought hope for clinical treatment for many patients with advanced renal cell carcinoma.however,the 5-year survival rate of advanced renal cell carcinoma is still not satisfactory.The early clinical manifestations of renal cell carcinoma are often not obvious,and most patients have already entered the middle and late stage when they see a doctor,so we urgently need more efficient and novel detection methods to improve the detection accuracy of renal cell carcinoma.In recent years,there are more and more studies related to tumor iron death.Different from other forms of cell death,such as apoptosis,necrosis and autophagy,iron death is a new type of programmed cell death characterized by iron-dependent accumulation of intracellular lipoid reactive oxygen species.With the continuous study of iron death,it has been determined that iron death plays a key role in killing tumor cells and inhibiting the growth of tumor cells,and there is evidence that renal cell carcinoma is closely related to iron death.Iron death can affect tumor cells through a variety of immune cells and immune factors,and iron death plays an important role in tumor cell clearance of renal clear cell carcinoma.However,its mechanism has not been clarified,and we need to reveal its significance in the treatment and prognosis of renal clear cell carcinoma through further research.We screened farnesyl-farnesyltransferase diphosphate(farnesyl-diphosphatefarnesyltransferase FDFT1),which is closely related to the prognosis of renal clear cell carcinoma,and verified their role in renal clear cell carcinoma in vitro.Clear cell renal cell carcinoma samples were collected to further verify the expression of FDFT1 in patients with renal clear cell carcinoma.Methods:In this study,the cancer gene map(The Cancer Genome Atlas,TCGA)was used to download the related sequencing data set of renal clear cell carcinoma cells and the retrieved iron death-related genes to analyze the differentially expressed genes.The iron death related genes were analyzed by univariate Cox regression model,and the iron death related gene FDFT1,which was closely related to the prognosis of renal clear cell carcinoma,was screened.The function of FDFT1 in 786 murine O cells was analyzed and detected by bioinformatics and plasmid transfection technique.The tumor tissue samples of patients with renal clear cell carcinoma and their adjacent tissues were collected and verified by real-time quantitative polymerase chain reaction and Western blotting analysis of FDFT1 gene expression.Results :1.44 differentially expressed genes related to iron death were obtained by differential analysis of iron death related genes.34 genes related to prognosis of renal clear cell carcinoma were obtained by univariate Cox regression model analysis,and22 prognostic iron death related genes were obtained by intersection between them.2.KEGG pathway analysis and GO functional enrichment analysis showed that the biological classification of prognostic iron death-related genes was enriched in sulfur compound biosynthesis,carboxylic acid biosynthesis,organic acid biosynthesis and sulfur metabolism.Hub gene and survival analysis showed that the high expression of FDFT1 was significantly correlated with better overall survival and disease-free survival,and FDFT1 may have an inhibitory effect on tumor growth.3.Western blotting and q PCR showed that the expression of FDFT1 was down-regulated in KIRC cell line 786 mur O,while FDFT1 was overexpressed,which could down-regulate the protein and m RNA levels of GPX4,a biomarker of iron death.Western blotting showed that the up-regulation of FDFT1 level could lead to the decrease of Akt expression.4.The overexpression of FDFT1 can significantly inhibit the proliferation,migration and invasion of renal clear cell carcinoma,and Western blotting and q RT-PCR show that the expression of FDFT1 in renal clear cell carcinoma is lower than that in normal tissues.Conclusion :Our study shows that FDFT1 participates in a lower expression level in renal clear cell carcinoma than in normal renal tissue,and the up-regulated expression of FDFT1 can help to inhibit the proliferation,migration and invasion of renal clear cell carcinoma.