The specific biomarkers of normal esophagus annotated from Human Proteome Atlas (HPA, https://www.proteinatlas.org), including GBP6, TGM1, TGM3, and S100A14, were overrepresented in the C1, which gradually decreased from the normal stage (stage 1) to advanced stages (stages 8 and 9) of ESCC (Kruskal–Wallis test, FDR < 2.2E–16, stage 9 vs. stage 1 ratio ≥ 2) (Supplementary Fig. 6h, i). This evidence concerns the gene S100A14 and esophageal squamous cell carcinoma.