In addition, based on the 4-Nitroquinoline 1-oxide (4-NQO)-induced primary ESCC model in esophageal epithelium-specific Notch1 knockout mice as described in our previous study,29 we also analyzed the difference in the microvascular density in 4-NQO-induced primary ESCC between Notch1+/+ and Notch1−/− mice, and the results showed that the microvascular density was significantly less in Notch1−/− tumors than that in Notch1+/+ tumors (Fig. 2g). This evidence concerns the gene NOTCH1 and esophageal squamous cell carcinoma.