Title
Comprehensive characterization of alternative splicing in renal cell carcinoma
Abstract
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.
Year
DOI
Venue
2021
10.1093/bib/bbab084
BRIEFINGS IN BIOINFORMATICS
Keywords
DocType
Volume
renal cell carcinoma, alternative splicing, subtype classification, pathway, immune
Journal
22
Issue
ISSN
Citations 
5
1467-5463
0
PageRank 
References 
Authors
0.34
0
12
Name
Order
Citations
PageRank
Yangjun Zhang100.34
Xiaoliang Wu200.34
Jingzhen Li300.34
Kui Sun400.34
Heng Li531.50
Libin Yan600.34
Chen Duan700.34
Haoran Liu800.34
Ke Chen900.34
Zhangqun Ye1000.34
Mugen Liu1100.34
Hua Xu1200.34