Irregular splicing was associated with tumor formation and progression in renal cell carcinoma (RCC) and many other cancers. By using splicing data in the TCGA SpliceSeq database, RCC subtype classification was performed and splicing features and their correlations with clinical course, genetic variants, splicing factors, pathways activation and immune heterogeneity were systemically analyzed. In this research, alternative splicing was found useful for classifying RCC subtypes. Splicing inefficiency with upregulated intron retention and cassette exon was associated with advanced conditions and unfavorable overall survival of patients with RCC. Splicing characteristics like splice site strength, guanine and cytosine content and exon length may be important factors disrupting splicing balance in RCC. Other than cis-acting and trans-acting regulation, alternative splicing also differed in races and tissue types and is also affected by mutation conditions, pathway settings and the response to environmental changes. Severe irregular splicing in tumor not only indicated terrible intra-cellular homeostasis, but also changed the activity of cancer-associated pathways by different splicing effects including isoforms switching and expression regulation. Moreover, irregular splicing and splicing-associated antigens were involved in immune reprograming and formation of immunosuppressive tumor microenvironment. Overall, we have described several clinical and molecular features in RCC splicing subtypes, which may be important for patient management and targeting treatment.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81874089]
语种:
外文
被引次数:
WOS:
PubmedID:
中科院(CAS)分区:
出版当年[2020]版:
大类|1 区生物
小类|1 区生化研究方法1 区数学与计算生物学
最新[2025]版:
大类|2 区生物学
小类|1 区数学与计算生物学2 区生化研究方法
JCR分区:
出版当年[2019]版:
Q1BIOCHEMICAL RESEARCH METHODSQ1MATHEMATICAL & COMPUTATIONAL BIOLOGY
最新[2023]版:
Q1BIOCHEMICAL RESEARCH METHODSQ1MATHEMATICAL & COMPUTATIONAL BIOLOGY
第一作者单位:[2]Tongji Hosp,Dept Urol,Wuhan,Peoples R China
通讯作者:
通讯机构:[1]Huazhong Univ Sci & Technol,Tongji Hosp,Tongji Med Coll,Dept Urol,Wuhan 430030,Peoples R China[*1]Inst Urol Hubei Prov, Wuhan 430030, Peoples R China
推荐引用方式(GB/T 7714):
Zhang Yangjun,Wu Xiaoliang,Li Jingzhen,et al.Comprehensive characterization of alternative splicing in renal cell carcinoma[J].BRIEFINGS IN BIOINFORMATICS.2021,22(5):doi:10.1093/bib/bbab084.
APA:
Zhang, Yangjun,Wu, Xiaoliang,Li, Jingzhen,Sun, Kui,Li, Heng...&Xu, Hua.(2021).Comprehensive characterization of alternative splicing in renal cell carcinoma.BRIEFINGS IN BIOINFORMATICS,22,(5)
MLA:
Zhang, Yangjun,et al."Comprehensive characterization of alternative splicing in renal cell carcinoma".BRIEFINGS IN BIOINFORMATICS 22..5(2021)