Taken together, a carcinogenesis path with eight dynamic waves in ESCC progression was revealed on the basis of the consistency among the genomic aberrations, proteomic alterations, and phosphoproteomic actions: metabolism (e.g., ANXA1 and CTSB) – DNA damage (e.g., PPP2R5A and SERPINB3) – cell proliferation (e.g., EGFR and EGF) – lesion invasion (e.g., GRB2 and PRKCB) – cell cycle (e.g., MCM2/3 and FGFR1OP) – cell differentiation (e.g., MSH3 and MTOR) – tumor metastasis (e.g., MMP2 and AKT2/3) – esophageal carcinogenesis (e.g., PGK1 and CTNNB1) (Supplementary Fig. 5k). The gene discussed is CTSB; the disease is esophageal squamous cell carcinoma.