Interestingly, based on the two proteomic clusters (C1 and C2) which were associated with the three phases in ESCC progression, the C2 (relatively malignant cluster) prominent mutation of AKAP9 upregulated the expression-level of AKAP9 and thus activated PKA, improving the transfer of ATP to ADP and enhancing glycolysis at the protein and phosphoprotein levels (Supplementary Fig. 9). Here, AKAP9 is linked to esophageal squamous cell carcinoma.