| [Background] As one of the common malignant tumors of the urinary system,renal cell carcinoma(RCC)has about 430,000 new cases worldwide each year,accounting for 2%-3% of all cancer cases.Among them,80%-90% of RCC patients are diagnosed with clear cell renal cell carcinoma(cc RCC),making cc RCC the major histological subtype of RCC.Patients with cc RCC have poor prognosis,which severely affects their health and wellbeing.In recent years,some immune checkpoint inhibitors,especially programmed death receptor-1(PD-1)and its ligand(PD-L1)inhibitors,have benefited some kidney cancer patients during treatment.However,the overall response rate of immunotherapy is less than 40%,meaning a significant proportion of patients cannot benefit from immunotherapy.Therefore,exploring the essential biological processes in cancer development,finding prognostic biomarkers,and identifying drugs sensitive to tumor treatment can effectively predict the survival and prognosis of kidney cancer patients.With the discovery of a new cell death process called "cuproptosis," researchers have turned their attention to this area.Cuproptosis is a novel,copper-dependent,and regulated cell death distinct from known RCD processes and is closely related to mitochondrial respiration.In our study,by integrating the gene expression dataset of cc RCC samples from The Cancer Genome Atlas(TCGA)database,we found significant differences in the expression of cuproptosis genes between cc RCC samples and normal kidney samples.Based on existing research,we hypothesize that the cuproptosis process may play a role in the development of cc RCC and attempt to construct a cuproptosis-related long noncoding RNA model to predict the prognosis of clear cell renal cell carcinoma and explore the changes in the immune microenvironment.[Objective] The expression profile of clear cell renal cell carcinoma gene in the TCGA database and the corresponding clinical data set were comprehensively mined to analyze the expression of cuproptosis gene in clear cell renal cell carcinoma.At the same time,ICGC database was used as external validation to construct a prognosis model of clear cell renal cell carcinoma based on cuproptosis related long chain non-coding RNA,providing a new perspective on the prognosis of clear cell renal cell carcinoma,immune cell invasion,and drug therapy.[Methods] By downloading the gene expression data and corresponding clinical data of patients with clear cell renal cell carcinoma from TCGA and ICGC databases and using R x64 4.1.3 for data analysis,the expression of cuproptosis related genes in clear cell renal cell carcinoma and normal samples was explored.The differential expression of cuproptosis regulator FDX1 in cc RCC cell lines and normal renal tubule cell lines was verified by Western Blot.After identifying the differential expression of cuproptosis gene in clear cell renal cell carcinoma,cuproptosis related Lnc RNAs were identified by coexpression analysis.Through univariate Cox analysis,Lasso regression analysis and multivariate Cox analysis of copper death Lnc RNAs,8 cuproptosis related Lnc RNAs were finally determined as prognostic model variables.In this model,principal component analysis,K-M survival analysis,C-index analysis,ROC analysis,column graph and tumor immune cell infiltration analysis were performed.[Results] Among the 19 known cuproptosis related genes,16 genes showed statistical difference in expression between cc RCC samples and normal samples,and the key regulatory factor FDX1 of cuproptosis was lower expressed in cc RCC cancer cell lines and higher expressed in normal cell lines,and the difference was statistically significant.The risk score of cuproptosis-related Lnc RNA prognostic model could be used as an independent prognostic factor to predict the survival time of cc RCC patients,and TIDE score,types of immune cell infiltration,and immune checkpoint gene expression were statistically different in the high and low risk group.[Conclusion] The differential expression of cuproptosis gene and the key regulatory factor FDX1 suggests that cuproptosis may play a role in the occurrence and development of cc RCC,establishing the association between cuproptosis and cc RCC,and laying a theoretical basis for the establishment of prognosis model based on cuproptosis.The prognosis model of cuproptosis-related Lnc RNA can better predict the survival prognosis and immunotherapy effect of patients with cc RCC.At the same time,it serves as an effective biomarker,demonstrating the differences in immune cell infiltration and immune checkpoint gene expression between high-risk and low-risk samples. |
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