Our results derived from bioinformatics analyses, in vivo and in vitro studies and clinical data indicate that CHRNA7 mediates nicotine-induced ESCC tumor-initiating capacity at least in part via activating the JAK2/STAT3/SOX2 signaling pathway, which has been proven to be frequently dysregulated in human ESCC [33]. This evidence concerns the gene CHRNA7 and esophageal squamous cell carcinoma.