Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan.
Sci Rep. 2012;2:584. doi: 10.1038/srep00584. Epub 2012 Aug 16.
Mounting evidence links cancers possessing stem-like properties with worse prognosis. Network biology with signal processing mechanics was explored here using expression profiles of a panel of tumor stem-like cells (TSLCs). The profiles were compared to their parental tumor cells (PTCs) and the human embryonic stem cells (hESCs), for the identification of gene chromobox homolog 5, CBX5, as a potential target for lung cancer. CBX5 was found to regulate the stem-like properties of lung TSLCs and was predictive of lung cancer prognosis. The investigation was facilitated by finding target genes based on modeling epistatic signaling mechanics via a predictive and scalable network-based survival model. Topologically-weighted measurements of CBX5 were synchronized with those of BIRC5, DNMT1, E2F1, ESR1, MLH1, MSH2, RB1, SMAD1 and TAF5. We validated our findings in another Taiwanese lung cancer cohort, as well as in knockdown experiments using sh-CBX5 RNAi both in vitro and in vivo.
越来越多的证据表明，具有干细胞样特性的癌症与更差的预后相关。本研究运用肿瘤干细胞样细胞（TSLCs）表达谱，结合信号处理力学的网络生物学，探讨了这一问题。将这些图谱与亲本肿瘤细胞（PTCs）和人类胚胎干细胞（hESCs）进行比较，鉴定出同源盒蛋白 5（CBX5）是肺癌的潜在靶点。研究发现 CBX5 可调节肺 TSLCs 的干细胞样特性，并可预测肺癌的预后。通过基于预测和可扩展的基于网络的生存模型，基于建模上位信号力学，发现靶基因，从而促进了这项研究。CBX5 的拓扑加权测量与 BIRC5、DNMT1、E2F1、ESR1、MLH1、MSH2、RB1、SMAD1 和 TAF5 的测量同步。我们在另一个台湾肺癌队列中以及在体外和体内使用 sh-CBX5 RNAi 进行的敲低实验中验证了我们的发现。
