Comprehensive analysis of aberrant alternative splicing related to carcinogenesis and prognosis of papillary thyroid cancer.
Comprehensive analysis of aberrant alternative splicing related to carcinogenesis and prognosis of papillary thyroid cancer.
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异常选择性剪接与甲状腺乳头状癌发生及预后相关的综合分析
DOI：
10.18632/aging.203608
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发表时间：
2021-10-08
期刊：
影响因子：
--
通讯作者：
Xu M
中科院分区：
文献类型：
--
作者：
Zheng X;Feng L;Yin Y;Yu C;He X;Zhu J;Zhang M;Yu J;Xu M
选择性剪接（alternative splicing，AS）作为一种重要的剪接机制，在肿瘤的发生、发展过程中起着重要的作用.然而，在乳头状甲状腺癌（PTC），全面的AS事件概况及其临床意义的数据是缺乏的。在此，使用来自癌症基因组图谱（TCGA）项目的389名PTC患者队列，使用RNA-Seq数据及其与匹配的临床信息的相关性进行全基因组AS事件分析。我们通过比较配对的肿瘤和邻近的健康组织，确定了1，925例癌症相关AS事件（CASE）。在这些通路中显著富集CASE的亲本基因与癌发生相关，如P53、KRAS、IL 6-JAK-STAT 3、细胞凋亡和MYC信号传导。AS的调控网络提示剪接因子的表达与CASE之间存在明显的相关性。我们确定了8个病例作为总生存期（OS）和无病生存期（DFS）的预测因子。基于DFS相关CASE建立的风险评分模型成功预测了PTC患者的预后。从无监督聚类分析结果，发现不同的聚类基础上的AS与预后，分子特征，免疫特性。总之，PTC中全面的全基因组AS景观分析显示了与肿瘤发生和预后相关的新AS事件，这为PTC的临床监测和治疗提供了新的见解。
As a key mechanism, alternative splicing (AS) plays a role in the cancer initiation and development. However, in papillary thyroid cancer (PTC), data for the comprehensive AS event profile and its clinical implications are lacking. Herein, a genome-wide AS event profiling using RNA-Seq data and its correlation with matched clinical information was performed using a 389 PTC patient cohort from the project of The Cancer Genome Atlas (TCGA). We identified 1,925 cancer-associated AS events (CASEs) by comparing paired tumors and neighboring healthy tissues. Parent genes with CASEs remarkably enriched in the pathways were linked with carcinogenesis, such as P53, KRAS, IL6-JAK-STAT3, apoptosis, and MYC signaling. The regulatory networks of AS implied an obvious correlation between the expression of splicing factor and CASE. We identified eight CASEs as predictors for overall survival (OS) and disease-free survival (DFS). The established risk score model based on DFS-associated CASEs successfully predicted the prognosis of PTC patients. From the unsupervised clustering analysis results, it is found that different clusters based on AS correlated with prognosis, molecular features, and immune characteristics. Taken together, the comprehensive genome-wide AS landscape analysis in PTC showed new AS events linked with tumorigenesis and prognosis, which provide new insights for clinical monitoring and therapy for PTC.
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影响因子：
14.9
作者：
Ritchie ME;Phipson B;Wu D;Hu Y;Law CW;Shi W;Smyth GK
通讯作者：
Smyth GK
DOI：
10.1038/nrclinonc.2017.88
发表时间：
2017-11
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Nishino M;Ramaiya NH;Hatabu H;Hodi FS
通讯作者：
Hodi FS
DOI：
10.1038/nrm.2017.27
发表时间：
2017-07
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Baralle FE;Giudice J
通讯作者：
Giudice J
影响因子：
82.9
作者：
Auslander N;Zhang G;Lee JS;Frederick DT;Miao B;Moll T;Tian T;Wei Z;Madan S;Sullivan RJ;Boland G;Flaherty K;Herlyn M;Ruppin E
通讯作者：
Ruppin E
影响因子：
4.7
作者：
Mao, Shuangshuang;Li, Yuan;He, Jie
通讯作者：
He, Jie