Epithelial–mesenchymal transition (EMT) is a complex nonlinear biological process that plays essential roles in fundamental biological processes such as embryogenesis, wounding healing, tissue regeneration, and cancer metastasis. A hallmark of EMT is the switch-like behavior during state transition, which is characteristic of phase transitions. Hence, detecting the tipping point just before mesenchymal state transition is critical for understanding molecular mechanism of EMT. Through dynamic network biomarkers (DNB) model, a DNB group with 37 genes was identified which can provide the early-warning signals of EMT. Particularly, we found that two DNB genes, i.e., SMAD7 and SERPINE1 promoted EMT by switching their regulatory network which was further validated by biological experiments. Survival analyses revealed that SMAD7 and SERPINE1 as DNB genes further acted as prognostic biomarkers for lung adenocarcinoma.

上皮-间质转化 (EMT) 是一个复杂的非线性生物学过程，在胚胎发生、伤口愈合、组织再生和癌症转移等基本生物学过程中起着至关重要的作用。EMT 的一个标志是状态转换期间的类似开关的行为，这是相变的特征。因此，检测间充质状态转变前的临界点对于理解 EMT 的分子机制至关重要。通过动态网络生物标志物（DNB）模型，鉴定出一个具有37个基因的DNB组，可以提供EMT的预警信号。特别是，我们发现两个 DNB 基因，即SMAD7和SERPINE1通过改变他们的监管网络来促进 EMT，这在生物学实验中得到了进一步验证。生存分析表明，作为 DNB 基因的SMAD7和SERPINE1进一步充当肺腺癌的预后生物标志物。