Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, 430072, China.
Medical Research Institute, School of Medicine, Wuhan University, Wuhan, 430071, China.
Oncogene. 2020 Jan;39(4):786-800. doi: 10.1038/s41388-019-1026-9. Epub 2019 Sep 23.
Although rRNA metabolism-related genes have been reported to be associated with human cancer, a systematic assessment of rRNA metabolism-related genes across human cancers is lacking. Thus, we performed a Pan-cancer analysis of rRNA metabolism-related genes across 20 human cancers. Here, we examined mRNA expression, mutation, DNA methylation, copy number variation (CNV) and clinical landscape of rRNA metabolism-related genes in more than 8600 patients across 20 human cancers from The Cancer Genome Atlas (TCGA) dataset. Besides, ten independent Gene Expression Omnibus (GEO) datasets, Cancer Cell Line Encyclopedia (CCLE) dataset and Project Achilles dataset were used to verify our study. A landscape of rRNA metabolism-related genes was established across 20 human cancers. The results suggest that rRNA metabolism-related genes are upregulated in multiple cancers, particularly in digestive and respiratory system cancers. Most of the upregulated genes were driven by CNV gain rather than mutation or DNA hypomethylation. We systematically identified CNV-driven rRNA metabolism-related genes with clinical relevance, including EXOSC8. Finally, functional experiments confirmed the oncogenic roles of EXOSC8 in colorectal carcinoma. Our study highlights the important roles of rRNA metabolism-related genes in tumorigenesis as prognostic biomarkers.
尽管已有研究报道 rRNA 代谢相关基因与人类癌症相关，但对人类癌症中 rRNA 代谢相关基因的系统评估仍存在空白。因此，我们针对 20 种人类癌症进行了 rRNA 代谢相关基因的泛癌症分析。在此，我们研究了来自癌症基因组图谱（TCGA）数据库的 20 种人类癌症中超过 8600 例患者的 rRNA 代谢相关基因的 mRNA 表达、突变、DNA 甲基化、拷贝数变异（CNV）和临床特征。此外，我们还使用了十个独立的基因表达综合数据库（GEO）、癌症细胞系百科全书（CCLE）数据集和 Project Achilles 数据集来验证我们的研究。建立了 20 种人类癌症中 rRNA 代谢相关基因的全景图。结果表明，rRNA 代谢相关基因在多种癌症中上调，特别是在消化系统和呼吸系统癌症中。大多数上调的基因是由 CNV 获得而不是突变或 DNA 低甲基化驱动的。我们系统地鉴定了具有临床相关性的 CNV 驱动的 rRNA 代谢相关基因，包括 EXOSC8。最后，功能实验证实了 EXOSC8 在结直肠癌中的致癌作用。我们的研究强调了 rRNA 代谢相关基因作为预后生物标志物在肿瘤发生中的重要作用。
