Gao Bo, Yu Tian, Xue Dongbo, Sun Boshi, Shao Qin, Choudhry Hani, Marcus Victoria, Ragoussis Jiannis, Zhang Yuguo, Zhang Weihui, Gao Zu-Hua
Department of General Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Pathology, The Research Institute of McGill University Health Center, Montreal, Québec, Canada.
PLoS One. 2017 Jun 19;12(6):e0178760. doi: 10.1371/journal.pone.0178760. eCollection 2017.
Approximately 9% of cancer-related deaths are caused by colorectal cancer. Liver metastasis is a major factor for the high colorectal cancer mortality rate. However, the molecular mechanism underlying colorectal cancer liver metastasis remains unclear. Using a global and multidimensional integration approach, we studied sequencing data, protein-protein interactions, and regulation of transcription factor and non-coding RNAs in primary tumor samples and liver metastasis samples to unveil the potential bridging molecules and the regulators that functionally link different stages of colorectal cancer liver metastasis. Primary tumor samples and liver metastasis samples had modules with significant overlap and crosstalk from which we identified several bridging genes (e.g. KNG1 and COX5B), transcription factors (e.g. E2F4 and CDX2), microRNAs (e.g. miR-590-3p and miR-203) and lncRNAs (e.g. lincIRX5 and lincFOXF1) that may play an important role in the process of colorectal cancer liver metastasis. This study enhances our understanding of the genetic alterations and transcriptional regulation that drive the metastatic process, but also provides the methodology to guide the studies on other metastatic cancers.
约9%的癌症相关死亡由结直肠癌导致。肝转移是结直肠癌死亡率高的主要因素。然而，结直肠癌肝转移的分子机制仍不清楚。我们采用全面且多维的整合方法，研究了原发性肿瘤样本和肝转移样本中的测序数据、蛋白质-蛋白质相互作用以及转录因子和非编码RNA的调控，以揭示潜在的桥梁分子以及在功能上连接结直肠癌肝转移不同阶段的调控因子。原发性肿瘤样本和肝转移样本具有显著重叠和相互作用的模块，从中我们鉴定出了几个可能在结直肠癌肝转移过程中发挥重要作用的桥梁基因（如KNG1和COX5B）、转录因子（如E2F4和CDX2）、微小RNA（如miR-590-3p和miR-203）和长链非编码RNA（如lincIRX5和lincFOXF1）。这项研究不仅增进了我们对驱动转移过程的基因改变和转录调控的理解，还提供了指导其他转移性癌症研究的方法。
