Hu Wangxiong, Yang Yanmei, Li Xiaofen, Zheng Shu
Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
Key Laboratory of Reproductive and Genetics, Ministry of Education, Women's Hospital, Zhejiang University, Hangzhou, Zhejiang 310006, China.
Oncotarget. 2017 Jan 24;8(4):6809-6818. doi: 10.18632/oncotarget.14303.
It is widely accepted that some messenger RNAs are evolutionarily conserved across species, both in sequence and tissue-expression specificity. To date, however, little effort has been made to exploit the transcriptome divergence between cancer and adjacent normal tissue at the pan-organ level. In this work, a transcriptome sequencing dataset from 675 normal-tumor pairs, representing 21 solid organs in The Cancer Genome Atlas, is used to evaluate expression evolution. The results show that in most cancer types, gene expression divergence and organ-specificity are reduced in cancer tissue compared to adjacent normal tissue. Furthermore, we observe that all cancers share cell cycle dysregulation through interrogating differentially expressed protein coding genes. Meanwhile, weighted correlation network analysis is used to detect of the gene module structure variation between cancer and adjacent normal tissue. And modules consisting of tightly co-regulated genes in cancer change substantially compared with those in adjacent normal tissue. We thus assume that the destruction of a coordinated regulatory network might result in tumorigenesis and tumor progression. Our results provide new insights into the complex cancer biology and shed light on the mysterious regulation mode for cancer.
人们普遍认为，一些信使核糖核酸在物种间具有进化保守性，在序列和组织表达特异性方面均如此。然而，迄今为止，在全器官水平利用癌症组织与相邻正常组织之间的转录组差异方面所做的工作甚少。在这项研究中，来自癌症基因组图谱中代表21种实体器官的675对正常-肿瘤组织的转录组测序数据集被用于评估表达进化。结果表明，在大多数癌症类型中，与相邻正常组织相比，癌症组织中的基因表达差异和器官特异性降低。此外，通过对差异表达的蛋白质编码基因进行分析，我们观察到所有癌症都存在细胞周期失调。同时，加权相关网络分析用于检测癌症组织与相邻正常组织之间基因模块结构的变化。与相邻正常组织相比，癌症中由紧密共调控基因组成的模块发生了显著变化。因此，我们推测协调调控网络的破坏可能导致肿瘤发生和肿瘤进展。我们的结果为复杂的癌症生物学提供了新的见解，并揭示了癌症神秘的调控模式。
