Integrative proteogenomic characterization of early esophageal cancer
Abstract We performed a comprehensive genomic, proteomic, and phosphoproteomic analysis of 756 trace-tumor-samples from 124 esophageal cancer (EC) patients, covering 9 major histopathological stages and 22 substages. The results revealed a significant diversity of proteome patterns in the 22 substages. The integrated multi-omics data identified genomic-proteomic aberrations revealing the association of TP53, ATM, and EP400 mutations that affected cell cycle, DNA repair, and glycolysis, with poor prognosis. Proteome-based analysis elucidated the stage-specific molecular characterization and defined the cancer-driving waves along with the mutation accumulation in esophageal carcinogenesis and progression. Furthermore, the trajectory analysis identified 6 major tracks related to different clinical features during early EC progression. Growingly enhanced and hyperphosphorylated phosphoglycerate kinase 1 (PGK1, S203) was detected and considered as a drug target in EC progression. Collectively, this study provides insight into the understanding of the molecular mechanism of EC progression and a valuable resource for the development of therapeutic targets.