Abstract
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.
Highlights
Esophageal cancer (EC) is the fourth most common cancer in China, with 375,000 annual deaths, 90% of which are esophageal squamous cell carcinoma (ESCC) (Chen et al, 2016)
The median of ESCC tumor mutation burden (TMB) of nonsilent mutation in the coding region was located between Uterine Corpus Endometrial Carcinoma (UCES) and Liver hepatocellular carcinoma (LIHC), and was lower than Esophageal adenocarcinoma (EAC) (Supplementary Figure S1)
The analysis of mutation signature has evolved from SBS to double-base substitution (DBS), insertions and deletion (ID) and other complex mutations (Alexandrov et al, 2020)
Summary
Esophageal cancer (EC) is the fourth most common cancer in China, with 375,000 annual deaths, 90% of which are esophageal squamous cell carcinoma (ESCC) (Chen et al, 2016). Due to the limited treatment methods, the 5 years survival rate of ESCC is less than 30% (Younes et al, 2002; Koshy et al, 2004). As a result of that, several ESCC driver genes had been identified. More than half of the Integrative ESCC Genomic Analyses driver genes were identified in only one cohort, and few biomarkers were identified as especial immunotherapyrelated biomarkers. Because of the lack of therapeutic targets for ESCC, targeted therapy treatment has not been improved significantly
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