van Tilborg Derek, Saccenti Edoardo
Laboratory of Systems and Synthetic Biology, Wageningen University & Research, Stippeneng, 6708 WE Wageningen, The Netherlands.
Cancers (Basel). 2021 Jan 21;13(3):393. doi: 10.3390/cancers13030393.
One of the major hallmarks of cancer is the derailment of a cell's metabolism. The multifaceted nature of cancer and different cancer types is transduced by both its transcriptomic and metabolomic landscapes. In this study, we re-purposed the publicly available transcriptomic and metabolomics data of eight cancer types (breast, lung, gastric, renal, liver, colorectal, prostate, and multiple myeloma) to find and investigate differences and commonalities on a pathway level among different cancer types. Topological analysis of inferred graphical Gaussian association networks showed that cancer was strongly defined in genetic networks, but not in metabolic networks. Using different statistical approaches to find significant differences between cancer and control cases, we highlighted the difficulties of high-level data-merging and in using statistical association networks. Cancer transcriptomics and metabolomics and landscapes were characterized by changed macro-molecule production, however, only major metabolic deregulations with highly impacted pathways were found in liver cancer. Cell cycle was enriched in breast, liver, and colorectal cancer, while breast and lung cancer were distinguished by highly enriched oncogene signaling pathways. A strong inflammatory response was observed in lung cancer and, to some extent, renal cancer. This study highlights the necessity of combining different omics levels to obtain a better description of cancer characteristics.
癌症的主要特征之一是细胞代谢紊乱。癌症的多面性以及不同的癌症类型是由其转录组学和代谢组学格局所传导的。在本研究中，我们重新利用了八种癌症类型（乳腺癌、肺癌、胃癌、肾癌、肝癌、结直肠癌、前列腺癌和多发性骨髓瘤）的公开转录组学和代谢组学数据，以在通路水平上寻找并研究不同癌症类型之间的差异和共性。对推断的图形高斯关联网络进行拓扑分析表明，癌症在遗传网络中得到了强烈定义，但在代谢网络中并非如此。使用不同的统计方法来找出癌症病例与对照病例之间的显著差异，我们强调了高级数据合并以及使用统计关联网络的困难。癌症转录组学和代谢组学以及格局的特征是大分子产生发生了变化，然而，仅在肝癌中发现了具有高度受影响通路的主要代谢失调。细胞周期在乳腺癌、肝癌和结直肠癌中富集，而乳腺癌和肺癌的特征是癌基因信号通路高度富集。在肺癌以及在一定程度上在肾癌中观察到强烈的炎症反应。本研究强调了结合不同组学水平以更好地描述癌症特征的必要性。
