PHEX and esophageal squamous cell carcinoma: To explore the transcriptomic alterations at various pathological stages during ESCC tumorigenesis, 8-week-old female C57BL/6 mice were treated with 4NQO for 16 weeks, which resulted in five recognizable precancerous and cancerous lesions in the esophagus, i.e., INF, HYP, DYS, CIS, and ICA (Fig. 1a; Supplementary Fig. 1a).