文章：

肾透明细胞癌肿瘤免疫浸润中的选择性剪接事件

Alternative splicing events in tumor immune infiltration in renal clear cell carcinomas 

原文发布日期：2022-04-04 

英文摘要：

Alternative splicing (AS) is a gene regulatory mechanism that drives protein diversity and dysregulation of AS plays a significant role in tumorigenesis. This study aimed to develop a prognostic signature based on AS and elucidate the role in tumor immune microenvironment (TIME) in clear cell renal cell carcinoma (ccRCC). The prognosis-related AS events were analyzed by univariate Cox regression analysis. Gene set enrichment analyses (GSEA) were performed for functional annotation. Prognostic signatures were identified and validated using univariate and multivariate Cox regression, LASSO regression, Kaplan–Meier survival analysis, and proportional hazards model. The context of TIME in ccRCC was also analyzed. Gene and protein expression data of C4orf19 were obtained from ONCOMINE website and Human Protein Altas. Splicing factors (SFs) regulatory networks were visualized. 4431 survival-related AS events in ccRCC were screened. Based on splicing subtypes, eight AS prognostic signatures were constructed. A nomogram with good prognostic prediction was generated. Furthermore, the prognostic signatures were significantly correlated with TIME diversity and immune checkpoint inhibitor (ICI)-related genes. C4orf19 was the only gene whose expression levels were downregulated among the prognostic AS-related genes, which is considered as a promising prognostic factor in ccRCC. Potential functions of SFs were determined by splicing regulatory networks. In our study, AS patterns of novel indicators for prognostic prediction of ccRCC were explored. The AS-SF networks provide information of regulatory mechanisms. Players of AS events related to TIME were investigated, which contribute to prognosis monitoring of ccRCC. 

摘要翻译： 

可变剪接（AS）是一种驱动蛋白质多样性的基因调控机制，其失调在肿瘤发生中起重要作用。本研究旨在基于AS构建肾透明细胞癌（ccRCC）的预后特征，并阐明其在肿瘤免疫微环境（TIME）中的作用。通过单变量Cox回归分析筛选与预后相关的AS事件，采用基因集富集分析（GSEA）进行功能注释，结合单多因素Cox回归、LASSO回归、Kaplan-Meier生存分析和比例风险模型建立并验证预后特征。同时分析了ccRCC中TIME的构成，从ONCOMINE数据库和人类蛋白质图谱获取C4orf19的基因及蛋白表达数据，可视化剪接因子（SFs）调控网络。共筛选出4431个ccRCC生存相关AS事件，基于剪接亚型构建了八种AS预后特征，生成具有良好预测性能的列线图。这些预后特征与TIME多样性及免疫检查点抑制剂（ICI）相关基因显著相关。C4orf19是预后相关AS基因中唯一表达下调的基因，被认为是ccRCC的潜在预后指标。通过剪接调控网络揭示了SFs的潜在功能，本研究探索了新型AS指标在ccRCC预后预测中的价值，AS-SF网络提供了调控机制信息，对TIME相关AS事件的解析为ccRCC预后监测提供了新视角。

原文链接：

Alternative splicing events in tumor immune infiltration in renal clear cell carcinomas