Zhuhong Hu, Zhenyu Bai, Xiangyuan Chen, Tingzhen Xu, Libin Song
The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang, China.
Department of Laboratory, General Hospital of Pingmei Shenma Medical Group, Henan, China.
Cancer Genet. 2019 Jan;230:58-65. doi: 10.1016/j.cancergen.2018.11.004. Epub 2018 Nov 13.
Last decades have witnessed the great progress in exploration of tumor transcriptome. However, most researches were restricted in gene-level expression. mRNA isoforms, especially tumor-specific isoforms have not been fully explored in tumor. Here, by analyzing RNA-seq data derived from hundreds of samples in TCGA projects, we comprehensively characterized the expression variations of mRNA isoforms in adenocarcinoma of lung (LUAD), which is one of leading causes of cancer-related death. Our analysis found that a variety of mRNA isoforms showed differential expression in LUAD tumor samples. Some of them even showed distinct variations compared to their host genes. Further analysis of functional enrichment revealed that up- and down-regulated mRNA isoforms took part in different types of biological process. In addition, we also identified hundreds of isoforms that expressed exclusively in LUAD tumor samples. Furthermore, the expression level of several isoforms, such as uc001kuk.3 and uc003yls.2, could separate tumor patients by overall survival periods. Our study provided new candidates for the diagnosis and prognosis of lung cancer.
过去几十年见证了肿瘤转录组探索方面的巨大进展。然而，大多数研究局限于基因水平的表达。信使核糖核酸（mRNA）异构体，尤其是肿瘤特异性异构体在肿瘤中尚未得到充分研究。在此，通过分析来自癌症基因组图谱（TCGA）项目数百个样本的RNA测序（RNA-seq）数据，我们全面表征了肺腺癌（LUAD）中mRNA异构体的表达变化，肺腺癌是癌症相关死亡的主要原因之一。我们的分析发现，多种mRNA异构体在LUAD肿瘤样本中表现出差异表达。其中一些与它们的宿主基因相比甚至表现出明显的差异。功能富集的进一步分析表明，上调和下调的mRNA异构体参与了不同类型的生物学过程。此外，我们还鉴定出数百种仅在LUAD肿瘤样本中表达的异构体。此外，几种异构体的表达水平，如uc001kuk.3和uc003yls.2，可以根据总生存期将肿瘤患者区分开来。我们的研究为肺癌的诊断和预后提供了新的候选指标。
