Signature of gene aberrant alternative splicing events in pancreatic adenocarcinoma prognosis.
Signature of gene aberrant alternative splicing events in pancreatic adenocarcinoma prognosis.
复制标题
胰腺腺癌预后中基因异常选择性剪接事件的特征
DOI：
10.7150/jca.48661
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发表时间：
2021
影响因子：
3.9
通讯作者：
Zhou J
中科院分区：
文献类型：
--
作者：
Yao J;Tang YC;Yi B;Yang J;Chai Y;Yin N;Zhang ZX;Wei YJ;Li DC;Zhou J
选择性剪接（alternative splicing，AS）作为一种有效而普遍的转录调控机制，参与了肿瘤的发生、发展过程。因此，系统分析胰腺癌的选择性剪接（PAAD）是必要的。从TCGA数据门户下载RNA-Seq数据和PAAD队列的相应临床信息。然后，使用Java应用程序SpliceSeq来评估RNA剪接模式并计算剪接百分比指数（PSI）。基于PAAD癌样品和邻近组织的正常样品之间的PSI值来鉴定差异表达的AS事件（DEAS）。Kaplan-Meier和考克斯回归分析用于评估DEAS与患者临床特征之间的关联。无监督聚类分析用于揭示具有不同生存模式的四个聚类。同时，GEO和TCGA结合GTEx验证AS基因和剪接因子的差异表达。经过严格筛选，共识别出45，313起AS事件，其中1，546起为差异表达的AS事件。19例DEAS与OS相关，5年总生存率为0.946。亚型聚类结果表明，个体AS的性质存在差异，影响临床结局。结果还确定了15个与PAAD预后相关的剪接因子。剪接因子ESRP 1和RBM 5在PAAD相关AS事件中起重要作用。PAAD相关的AS事件，剪接网络，并在这项研究中确定的集群是有价值的破译AS在PAAD的潜在机制，并可能有助于建立进一步验证的治疗目标。
Alternative splicing (AS), as an effective and universal mechanism of transcriptional regulation, is involved in the development and progression of cancer. Therefore, systematic analysis of alternative splicing in pancreatic adenocarcinoma (PAAD) is warranted. The corresponding clinical information of the RNA-Seq data and PAAD cohort was downloaded from the TCGA data portal. Then, a java application, SpliceSeq, was used to evaluate the RNA splicing pattern and calculate the splicing percentage index (PSI). Differentially expressed AS events (DEAS) were identified based on PSI values between PAAD cancer samples and normal samples of adjacent tissues. Kaplan-Meier and Cox regression analyses were used to assess the association between DEAS and patient clinical characteristics. Unsupervised cluster analysis used to reveal four clusters with different survival patterns. At the same time, GEO and TCGA combined with GTEx to verify the differential expression of AS gene and splicing factor. After rigorous filtering, a total of 45,313 AS events were identified, 1,546 of which were differentially expressed AS events. Nineteen DEAS were found to be associated with OS with a five-year overall survival rate of 0.946. And the subtype clusters results indicate that there are differences in the nature of individual AS that affect clinical outcomes. Results also identified 15 splicing factors associated with the prognosis of PAAD. And the splicing factors ESRP1 and RBM5 played an important role in the PAAD-associated AS events. The PAAD-associated AS events, splicing networks, and clusters identified in this study are valuable for deciphering the underlying mechanisms of AS in PAAD and may facilitate the establishment of therapeutic goals for further validation.
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影响因子：
5.7
作者：
Matsuda Y;Yoshimura H;Suzuki T;Uchida E;Naito Z;Ishiwata T
通讯作者：
Ishiwata T
影响因子：
3.8
作者：
Arafat H;Lazar M;Salem K;Chipitsyna G;Gong Q;Pan TC;Zhang RZ;Yeo CJ;Chu ML
通讯作者：
Chu ML
影响因子：
4
作者：
Mao, Shuangshuang;Li, Yuan;He, Jie
通讯作者：
He, Jie
DOI：
10.1261/rna.066712.118
发表时间：
2018-10
期刊：
RNA (New York, N.Y.)
影响因子：
--
作者：
Harvey SE;Xu Y;Lin X;Gao XD;Qiu Y;Ahn J;Xiao X;Cheng C
通讯作者：
Cheng C
影响因子：
5.3
作者：
Munkley J;Livermore K;Rajan P;Elliott DJ
通讯作者：
Elliott DJ