Comprehensive characterization of alternative splicing in renal cell carcinoma.
Brief Bioinform
; 22(5)2021 09 02.
Article
en En
| MEDLINE
| ID: mdl-33822848
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Carcinoma de Células Renales
/
Biomarcadores de Tumor
/
Empalme Alternativo
/
Neoplasias Renales
/
Mutación
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Brief Bioinform
Asunto de la revista:
BIOLOGIA
/
INFORMATICA MEDICA
Año:
2021
Tipo del documento:
Article
País de afiliación:
China