Departments of Urology, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China.
Aging (Albany NY). 2020 Mar 26;12(6):4996-5009. doi: 10.18632/aging.102924.
To explore the correlations among alternative splicing (AS), splicing factors (SF) and survival outcome in adrenocortical carcinoma (ACC) patients.
A total of 92 ACC patients were included. Univariate analysis identified 3919 AS events significantly associated with overall survival. Lasso method followed by multivariate analysis revealed that the prognostic capacity of these survival-related AS events is satisfactory. Interestingly, we found that the area under the curve (AUC) of AA, AD, AP and RI were more than 0.9, indicating that these four types of AS were of great significance. Independent prognostic analysis showed that only the risk score was the independent risk factor of ACC survival. Finally, we constructed an interesting interaction network between AS and SF.
This is the first and most comprehensive study to explore the aberrant AS variants in ACC, which might provide novel insights into molecular mechanism of ACC.
The transcriptome data, clinical information and Percent Spliced In (PSI) values of the ACC were obtained from TCGA database and TCGA SpliceSeq data portal. Lasso method and uni/multivariate Cox regression analysis were used to identify survival-related AS events and develop multi-AS-based signatures. The relationship between AS events and SFs was also investigated.
探讨肾上腺皮质癌（ACC）患者中可变剪接（AS）、剪接因子（SF）与生存结局的相关性。
共纳入 92 例 ACC 患者。单因素分析确定了 3919 个与总生存显著相关的 AS 事件。Lasso 法和多因素分析进一步揭示了这些与生存相关的 AS 事件具有良好的预后预测能力。有趣的是，我们发现 AA、AD、AP 和 RI 的曲线下面积（AUC）均大于 0.9，提示这四种 AS 类型具有重要意义。独立预后分析表明，只有风险评分是 ACC 生存的独立危险因素。最后，我们构建了一个有趣的 AS 与 SF 之间的互作网络。
这是首个也是最全面的探讨 ACC 中异常 AS 变异的研究，可能为 ACC 的分子机制提供新的见解。
从 TCGA 数据库和 TCGA SpliceSeq 数据门户获取了 ACC 的转录组数据、临床信息和 PSI 值。采用 Lasso 法和单/多因素 Cox 回归分析筛选与生存相关的 AS 事件，并构建基于多 AS 的预后模型。还研究了 AS 事件与 SF 之间的关系。
