The Cancer Genome Atlas (TCGA) project produced RNA-Seq data for tens of thousands of cancer and non-cancer samples with clinical survival information, providing an unprecedented opportunity for analyzing prognostic genes and their isoforms. In this study, we performed the first large-scale identification of transcriptional isoforms that are specifically associated with patient prognosis, even without gene-level association. These specific isoforms are defined as Transcripts Associated with Patient Prognosis (TAPPs). Although a group of TAPPs are the principal isoforms of their genes with intact functional protein domains, another group of TAPPs lack important protein domains found in their canonical gene isoforms. This dichotomy in the distribution of protein domains may indicate different patterns of TAPPs association with cancer. TAPPs in protein-coding genes, especially those with altered protein domains, are rich in known cancer driver genes. We further identified multiple types of cancer recurrent TAPPs, such as DCAF17-201, providing a new approach for the detection of cancer-associated events. In order to make the wide research community to study prognostic isoforms, we developed a portal named GESUR (http://gesur.cancer-pku.cn/), which illustrates the detailed prognostic characteristics of TAPPs and other isoforms. Overall, our integrated analysis of gene expression and clinical parameters provides a new perspective for understanding the applications of different gene isoforms in tumor progression.

癌症基因组图谱（TCGA）项目提供了具有临床生存信息的成千上万个癌症和非癌症样品的RNA-Seq数据，为分析预后基因及其同工型提供了前所未有的机会。在这项研究中，我们首次大规模鉴定了与患者预后特别相关的转录亚型，即使没有基因水平的关联。这些特定的同工型定义为与患者预后相关的转录本（TAPP）。尽管一组TAPPs是其具有完整功能蛋白结构域的基因的主要同工型，但另一组TAPPs缺乏在其规范基因同工型中发现的重要蛋白结构域。蛋白质结构域分布的这种二分法可能表明TAPPs与癌症相关的不同模式。蛋白质编码基因中的TAPP，特别是那些具有改变的蛋白质结构域的TAPP，富含已知的癌症驱动基因。我们进一步确定了多种类型的癌症复发性TAPP，例如DCAF17-201，提供了一种检测癌症相关事件的新方法。为了使广泛的研究团体能够研究预后亚型，我们开发了一个名为GESUR的门户网站（http://gesur.cancer-pku.cn/），该门户网站阐明了TAPPs和其他亚型的详细预后特征。总体而言，我们对基因表达和临床参数的综合分析为理解不同基因同工型在肿瘤进展中的应用提供了新的视角。