Research On Recognition And Functional Analysis Of Splicing Isoforms Associated With Kidney Renal Clear Cell Carcinoma

Renal cell carcinoma is considered to be a malignant tumor with a high incidence of urinary system,and kidney renal clear cell carcinoma(KIRC)is the most common subtype of renal malignant tumor.Although the treatment of renal clear cell carcinoma has made great progress,its mortality rate is still very high,especially for patients with advanced/metastatic renal clear cell carcinoma,the current efficacy of immunotherapy and molecular targeted drugs is not ideal.Cancer-related abnormal alternative splicing analysis is an important research direction for cancer target search in recent years.Alternative splicing causes abnormal protein production or overexpression.These proteins regulate the cell cycle,apoptosis and other life processes,leading to the occurrence and development of cancer.However,there is a lack of comprehensive analysis of the effect of alternative splicing on renal clear cell carcinoma.Therefore,in order to improve the prognostic effect of patients with renal clear cell carcinoma,further improve the biomarkers used for prognosis prediction and treatment of patients with renal clear cell carcinoma,so as to screen potential diagnostic therapeutic targets for KIRC treatment.Relevant variable splicing isoforms and their functional roles are thoroughly explored,mainly divided into the following three aspects.First,in order to screen for differential alternative splicing events(DASEs)between para-cancer and cancer samples in KIRC,this paper included 252 samples into this study cohort based on RNA-Seq data provided by TCGA.A total of 35 436 alternative splicing events were detected in the cohort and 604 DASEs were identified.Most of the genes related to alternative splicing produced more than two alternative splicing isoforms.Secondly,in order to study the potential functions of DASEs and explore their impact on the occurrence and development of KIRC,this paper comprehensively analyzes the functions of DASEs through GO enrichment analysis,tumor immune infiltration analysis,splicing factor correlation analysis,and survival analysis to reveal The DASEs parental gene was significantly enriched in the pathways related to KIRC and cancer cell metastasis,and a splicing factor-related regulatory network was constructed.It was found that the RASGEF1 A gene that plays a role in cell migration produces an isoform after infiltration with KIRC,The proportion of sexual Tlymphocytes is significantly related.In addition,this paper screens 40 DASEs that are significantly related to the survival time of KIRC patients.Finally,in order to further analyze the effect of alternative splicing in KIRC on cancer cell metastasis,this paper established a KIRC stemness index m RNAsi prediction model based on a class of logistic regression algorithms through stem cell RNA-Seq data provided by PCBC database,and further revealed The potential regulatory mechanism of alternative splicing in KIRC samples with different degrees of dedifferentiation.This paper takes the KIRC sample provided by TCGA as the research object,identifies the differential alternative splicing events in KIRC,comprehensively analyzes the alternative splicing events related to KIRC,and screens the DASEs which are significantly correlated with immune microenvironment,the survival time and the stemness indices of KIRC.This paper helps to study the mechanism of alternative splicing in the occurrence of KIRC,and provides a reference for identifying potential clinical biomarkers and therapeutic targets.It has important theoretical significance and application value.