Alternative splicing events are prognostic in hepatocellular carcinoma
Alternative splicing events are prognostic in hepatocellular carcinoma
复制标题
选择性剪接事件可预测肝细胞癌的预后
DOI：
10.18632/aging.102085
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发表时间：
2019-07-15
期刊：
影响因子：
5.2
通讯作者：
Huang, Zi-Lin
中科院分区：
文献类型：
--
作者：
Chen, Qi-Feng;Li, Wang;Huang, Zi-Lin
选择性剪接事件（ase）在癌症的发生和发展中起着重要作用。我们研究了ase是否对肝细胞癌（HCC）的总生存期（OS）有预后影响。获得了癌症基因组图谱中343例患者的RNA测序数据。然后从TCGASpliceSeq数据库中获得这些患者的匹配剪接事件数据，该数据库包括7种类型的ase数据。单因素和多因素Cox回归分析显示，3814例OS相关剪接事件（OS- ses）与OS相关。根据最显著的OS-SEs制定预后指标。与基于单一ASE类型的预后指数相比，基于所有7种ASE类型的预后指数（PI-ALL）在预测HCC患者2000天OS方面显示出更高的疗效。根据中位预后指数将患者分为高危组和低危组。Kaplan-Meier生存分析表明，PI-ALL具有最大的区分预后良好与不良患者的能力。最后，单因素Cox回归分析显示，23个剪接因子的表达与HCC队列中OS-SEs相关。我们的数据表明，基于ase的预后指标是HCC中OS的预后指标。
Alternative splicing events (ASEs) play a role in cancer development and progression. We investigated whether ASEs are prognostic for overall survival (OS) in hepatocellular carcinoma (HCC). RNA sequencing data was obtained for 343 patients included in The Cancer Genome Atlas. Matched splicing event data for these patients was then obtained from the TCGASpliceSeq database, which includes data for seven types of ASEs. Univariate and multivariate Cox regression analysis demonstrated that 3,814 OS-associated splicing events (OS-SEs) were correlated with OS. Prognostic indices were developed based on the most significant OS-SEs. The prognostic index based on all seven types of ASEs (PI-ALL) demonstrated superior efficacy in predicting OS of HCC patients at 2,000 days compared to those based on single ASE types. Patients were stratified into two risk groups (high and low) based on the median prognostic index. Kaplan-Meier survival analysis demonstrated that PI-ALL had the greatest capacity to distinguish between patients with favorable vs. poor outcomes. Finally, univariate Cox regression analysis demonstrated that the expression of 23 splicing factors was correlated with OS-SEs in the HCC cohort. Our data indicate that a prognostic index based on ASEs is prognostic for OS in HCC.