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Due to the lack of effective diagnostic markers and therapeutic targets, esophageal squamous cell carcinoma (ESCC) shows a poor 5 years survival rate of less than 30%. To explore the potential therapeutic targets of ESCC, we integrated and reanalyzed the mutation data of WGS (whole genome sequencing) or WES (whole exome sequencing) from a total of 1,145 samples in 7 large ESCC cohorts, including 270 ESCC gene expression data. Two new mutation signatures and 20 driver genes were identified in our study. Among them,  AP3S1 ,  MUC16 , and  RPS15  were reported for the first time. We also discovered that the  KMT2D  was associated with the multiple clinical characteristics of ESCC, and  KMT2D  knockdown cells showed enhanced cell migration and cell invasion. Furthermore, a few neoantigens were shared between ESCC patients. For ESCC, compared to TMB, neoantigen might be treated as a better immunotherapy biomarker. Our research expands the understanding of ESCC mutations and helps the identification of ESCC biomarkers, especially for immunotherapy biomarkers.

Integrative Genomic Analyses of 1,145 Patient Samples Reveal New Biomarkers in Esophageal Squamous Cell Carcinoma