We demonstrated the hub genes (IGF2, SCD, GALNT1, TLCD1, SHISA9, NLGN1, F13A1, ADAMTS8, GIF, PLD5, SLC13A3, ORM1, BTNL9, PGA5, and PGA4, and RPL5, FGA, and EBF4) were related to clinical and pathological indices, including gender, anatomical subdivisions, reflux history and Barrett esophagus, histological grade, pathological stages, and TNM stages. Here, SHISA9 is linked to Barrett esophagus.