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Comprehensive characterization of alternative splicing in renal cell carcinoma

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单位: [1]Huazhong Univ Sci & Technol,Tongji Hosp,Tongji Med Coll,Dept Urol,Wuhan 430030,Peoples R China [2]Tongji Hosp,Dept Urol,Wuhan,Peoples R China [3]Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Key Lab Mol Biophys, Minist Educ, Wuhan, Peoples R China [4]Zhejiang Univ, Affiliated Hosp 1, Sch Med, Dept Urol, Hangzhou, Peoples R China [5]Kunming Med Univ, Affiliated Hosp 2, Dept Urol, Kunming, Yunnan, Peoples R China
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关键词: renal cell carcinoma alternative splicing subtype classification pathway immune

摘要:
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.

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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
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出版当年[2019]版:
Q1 BIOCHEMICAL RESEARCH METHODS Q1 MATHEMATICAL & COMPUTATIONAL BIOLOGY
最新[2023]版:
Q1 BIOCHEMICAL RESEARCH METHODS Q1 MATHEMATICAL & COMPUTATIONAL BIOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2019版] 出版当年五年平均 出版前一年[2018版] 出版后一年[2020版]

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第一作者单位: [2]Tongji Hosp,Dept Urol,Wuhan,Peoples R China
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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
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