Screening Of Cuproptosis-related LncRNAs To Construct A Prognostic Models Of KIRC Based On Bioinformatics

Objective: Renal clear cell carcinoma data in TCGA database were analyzed by bioinformatics methods to screen cuproptosis-related lnc RNAs for constructing a prognositc model.The relationship between this model and immunotherapy effects as well as drug sensitivity was explored.Methods:(1)RNA-seq data,clinical data and SNV data of renal clear cell carcinoma were downloaded from TCGA database,and lnc RNA expression matrix were obtained.The genes were annotated by Perl software and distinguished into m RNA and lnc RNA,and then co-expression analysis of cuproptosis-related genes and lnc RNAs was performed to obtain cuproptosis-related lnc RNA.(2)The survival time,survival status and lnc RNA expression data of renal clear cell carcinoma samples were merged to obtain the all set,which was randomly divided into training set and testing set in a 1:1 ratio.Through univariate Cox analysis,Lasso regression analysis and multivariate Cox analysis of cuproptosis-related lnc RNAs in the training set,14 risk lnc RNAs were finally identified to construct a prognostic model,which was validated in the testing set and all set.(3)The median risk score of the training set was used as the cut-off threshold to divide samples into high-and low-risk groups.The overall survival analysis,progression-free survival analysis,subgroup survival analysis,principal component analysis,independent prognostic analysis,C-index analysis,ROC curve analysis,tumor gene mutation analysis and nomogram were used to verify the ability to predict prognosis and distinguish different risk groups.(4)Differential expressed gene analysis and gene set enrichment analysis were performed on the high-and low-risk groups to observe the signal pathways and functions of differential genes.(5)Ss GSEA and CIBERSORT algorithms were used to evaluate the differences in immune cell infiltration,immune function score and immune checkpoint gene expression score between the high-and low-risk groups.The relationship between this model and TMB,TME,and immunotherapy reaction in renal clear cell carcinoma samples was also predicted.(6)Finally,Cell Miner database was used to reveal the relationship between sensitivity of anti-tumor drugs and risk lnc RNAs constructing the model.The IC50 values of anti-tumor drugs in GDSC database in different risk groups were predicted,and the sensitive drugs with potential therapeutic value for KIRC were screened out.Results:(1)A total of 1028 cuproptosis-related lnc RNAs were screened from TCGA-KIRC transcriptome data,of which 361 lnc RNAs were significantly related to the prognosis of patients(p<0.05).(2)We established a risk prognosis model constructed by 14 cuproptosis-related lnc RNAs,which was verified to be effective in distinguishing different risk populations and clinicopathological characteristics,and had good survival predictive ability.(3)The differentially expressed genes between high-and low-risk groups were mainly enriched in the biological process of humoral immune response mediated by circulating immunoglobulins,cytokine-cytokine receptor interaction,complement and coagulation cascade and other metabolic pathways,which may be the key pathways in regulating biological behaviors such as proliferation,invasion and metastasis of KIRC tumor cells for cuproptosis-related lnc RNAs.(4)In the high-risk group,there are more immune cells infiltrating in the TME,and scores of immune function or immune checkpoint gene expression tend to be higher.The TMB and risk of immunotherapy escape in the high-risk group is higher,while the tumor purity is lower.(5)The expression level of risk lnc RNAs in NCI-60 cell line was significantly correlated with sensitivity of 51 anticancer drugs,and IC50 values of 68 anticancer drugs in GDSC database showed significant differences between the high-and low-risk groups.Conclusion: The risk prognosis model constructed of cuproptosis-related lnc RNAs in this study can distinguish high-and low-risk groups of KIRC patients,and predict prognosis,clinicopathological characteristics and immunotherapy efficacy,which has certain clinical application value.At the same time,a variety of potential therapeutic drugs for KIRC were screened,which are worthy of further exploration.