National Clinical Research Center of Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.
Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
Oncol Rep. 2018 Oct;40(4):2014-2022. doi: 10.3892/or.2018.6623. Epub 2018 Aug 2.
Alternative mRNA splicing (AS) contributes greatly to expanding the diversity and function of the proteome. Increasing evidence has suggested that dysregulation of mRNA splicing may be associated with various types of cancer. In the present study, RNA sequencing data were used to investigate alterations to the global mRNA splicing landscape of cellular genes from 452 stomach adenocarcinoma (STAD) tissues available in The Cancer Genome Atlas. Seven types of AS events, including the profiles of exon skipping events, were analyzed using SpliceSeq software. A total of 60,754 AS events in 10,611 genes were detected, more than half of which were exon skipping events. The AS events were compared between 415 STAD tissues and 37 normal tissues, and 3,895 differentially spliced cancer-specific events were identified. In addition, the association of the AS events with the overall survival of 373 STAD patients was analyzed. Multivariate Cox regression analysis revealed that prognosis prediction models based on the AS events with clinical parameters had an excellent performance in predicting the survival of STAD patients. This study provides a comprehensive portrait of global changes in mRNA splicing signatures that occur in gastric cancer. These results allowed the identification of a core set of AS in gastric cancer and indicated that AS events may serve as prognostic indicators.
可变剪接（AS）极大地促进了蛋白质组的多样性和功能扩展。越来越多的证据表明，mRNA 剪接的失调可能与各种类型的癌症有关。在本研究中，我们使用 RNA 测序数据，从癌症基因组图谱（TCGA）中 452 例胃腺癌（STAD）组织中，研究了细胞基因中全局 mRNA 剪接图谱的改变。使用 SpliceSeq 软件分析了七种类型的 AS 事件，包括外显子跳跃事件的特征。在 10611 个基因中检测到 60754 个 AS 事件，其中一半以上为外显子跳跃事件。将 415 例 STAD 组织和 37 例正常组织中的 AS 事件进行比较，鉴定出 3895 个差异剪接的癌症特异性事件。此外，还分析了 AS 事件与 373 例 STAD 患者总生存期的关系。多变量 Cox 回归分析显示，基于 AS 事件和临床参数的预后预测模型在预测 STAD 患者的生存方面具有优异的性能。本研究提供了胃癌中全局 mRNA 剪接特征变化的综合图谱。这些结果确定了胃癌中一组核心的 AS，并表明 AS 事件可能作为预后指标。
