| Renal cell carcinoma is a common malignant tumor,of which kidney renal clear cell carcinoma（KIRC）accounts for about 75%and is the most common type of renal cell carcinoma.KIRC has a low survival rate and currently lacks potent immune checkpoint and targeted therapy inhibitors.Alternative splicing（AS）is a new biomarker and therapeutic target for cancer.Combining transcription factors（TFs）and RNA-binding proteins（RBPs）in renal cancer to explore the regulatory mechanism of alternative splicing and to discover effective biomarkers or therapeutic targets for renal cancer patients.In this essay,feature selection is firstly carried out based on statistical methods,which is mainly divided into two steps.The first step is to use the combined algorithm of Mutual information-Sure independence screening-LASSO（MI-ISIS-LASSO）,from a large number of alternative splicing events（ASEs）in renal cancer The second step is to combine the Wilcoxon rank sum test and the Log2Fold Change（Log2FC）differential analysis method to perform differential analysis of RNA-binding protein and transcription factors respectively,and select the RNA-binding proteins and transcription factors specifically expressed in renal cancer.Then,in order to discover transcription factor,RNA-binding protein,and ASE with potential regulatory relationships,a linear mixed-effects model was constructed to identify the TF-RBP-AS triplet,and according to the transcription factor abundance and the correlation change of RNA-binding protein expression and the level of PSI targeting alternative splicing to discriminate the triplet function.Finally,validation and application studies of triplet interactions were performed to analyze the possible regulatory relationship between the triplet and to verify the prognostic value of the triplet.The results show that the regulatory network between transcription factor,RNA-binding protein and alternative splicing is very complex,and the triplet network reveals the relationship between RNA-binding protein and transcription factor in the process of alternative splicing dysregulation to a certain extent;TF-RBP-AS triplet plays a role in renal cancer compared with single transcription factors,RNA-binding protein and alternative splicing,the triplet has better prognostic value and is expected to become a new renal cancer biomarker or therapeutic target.The innovation of this paper mainly has the following two points:（1）Linear mixed effects model is established to study the regulatory network of transcription factor,RNA-binding protein and alternative splicing in renal cancer;（2）Combining RNA-binding protein and transcription factor into the research of alternative splicing in renal cancer,which is the basis for alternative splicing The research provided a new perspective;and the triplet has the potential as a biomarker or therapeutic target for kidney cancer,which may help the treatment of kidney cancer. |
