Background:Clear-cell renal cell carcinoma(ccRCC)is the most common malignant kidney cancer.However,the tumor microenvironment and crosstalk involved in metabolic reprogramming in ccRCC are not well-understood.Methods...Background:Clear-cell renal cell carcinoma(ccRCC)is the most common malignant kidney cancer.However,the tumor microenvironment and crosstalk involved in metabolic reprogramming in ccRCC are not well-understood.Methods:We used The Cancer Genome Atlas to obtain ccRCC transcriptome data and clinical information.The EMTAB-1980 cohort was used for external validation.The GENECARDS database contains the first 100 solute carrier(SLC)-related genes.The predictive value of SLC-related genes for ccRCC prognosis and treatment was assessed using univariate Cox regression analysis.An SLC-related predictive signature was developed through Lasso regression analysis and used to determine the risk profiles of patients with ccRCC.Patients in each cohort were separated into high-and low-risk groups based on their risk scores.The clinical importance of the signature was assessed through survival,immune microenvironment,drug sensitivity,and nomogram analyses using R software.Results:SLC25A23,SLC25A42,SLC5A1,SLC3A1,SLC25A37,SLC5A6,SLCO5A1,and SCP2 comprised the signatures of the eight SLCrelated genes.Patients with ccRCC were separated into high-and low-risk groups based on the risk value in the training and validation cohorts;the high-risk group had a significantly worse prognosis(p<0.001).The risk score was an independent predictive indicator of ccRCC in the two cohorts according to univariate and multivariate Cox regression(p<0.05).Analysis of the immune microenvironment showed that immune cell infiltration and immune checkpoint gene expression differed between the two groups(p<0.05).Drug sensitivity analysis showed that compared to the low-risk group,the high-risk group was more sensitive to sunitinib,nilotinib,JNK-inhibitor-VIII,dasatinib,bosutinib,and bortezomib(p<0.001).Survival analysis and receiver operating characteristic curves were validated using the E-MTAB-1980 cohort.Conclusions:SLC-related genes have predictive relevance in ccRCC and play roles in the immunological milieu.Our results provide insight into metabolic reprogramming in ccRCC and identify promising treatment targets for ccRCC.展开更多
基金supported by the National Natural Science Foundation of China[Grant Numbers 82170769,81900684,and 81870512].
文摘Background:Clear-cell renal cell carcinoma(ccRCC)is the most common malignant kidney cancer.However,the tumor microenvironment and crosstalk involved in metabolic reprogramming in ccRCC are not well-understood.Methods:We used The Cancer Genome Atlas to obtain ccRCC transcriptome data and clinical information.The EMTAB-1980 cohort was used for external validation.The GENECARDS database contains the first 100 solute carrier(SLC)-related genes.The predictive value of SLC-related genes for ccRCC prognosis and treatment was assessed using univariate Cox regression analysis.An SLC-related predictive signature was developed through Lasso regression analysis and used to determine the risk profiles of patients with ccRCC.Patients in each cohort were separated into high-and low-risk groups based on their risk scores.The clinical importance of the signature was assessed through survival,immune microenvironment,drug sensitivity,and nomogram analyses using R software.Results:SLC25A23,SLC25A42,SLC5A1,SLC3A1,SLC25A37,SLC5A6,SLCO5A1,and SCP2 comprised the signatures of the eight SLCrelated genes.Patients with ccRCC were separated into high-and low-risk groups based on the risk value in the training and validation cohorts;the high-risk group had a significantly worse prognosis(p<0.001).The risk score was an independent predictive indicator of ccRCC in the two cohorts according to univariate and multivariate Cox regression(p<0.05).Analysis of the immune microenvironment showed that immune cell infiltration and immune checkpoint gene expression differed between the two groups(p<0.05).Drug sensitivity analysis showed that compared to the low-risk group,the high-risk group was more sensitive to sunitinib,nilotinib,JNK-inhibitor-VIII,dasatinib,bosutinib,and bortezomib(p<0.001).Survival analysis and receiver operating characteristic curves were validated using the E-MTAB-1980 cohort.Conclusions:SLC-related genes have predictive relevance in ccRCC and play roles in the immunological milieu.Our results provide insight into metabolic reprogramming in ccRCC and identify promising treatment targets for ccRCC.
