Key Genetic Determinants Driving Esophageal Squamous Cell Carcinoma Initiation and Immune Evasion.

ABSTRACT:

Background & aims

Despite recent progress in identifying aberrant genetic and epigenetic alterations in esophageal squamous cell carcinoma (ESCC), the mechanism of ESCC initiation remains unknown.

Methods

Using CRISPR/Cas 9-based genetic ablation, we targeted 9 genes (TP53, CDKN2A, NOTCH1, NOTCH3, KMT2D, KMT2C, FAT1, FAT4, and AJUBA) in murine esophageal organoids. Transcriptomic phenotypes of organoids and chemokine released by organoids were analyzed by single-cell RNA sequencing. Tumorigenicity and immune evasion of organoids were monitored by allograft transplantation. Human ESCC single-cell RNA sequencing data sets were analyzed to classify patients and find subsets relevant to organoid models and immune evasion.

Results

We established 32 genetically engineered e

SUBMITTER: Ko KP 

PROVIDER: S-EPMC10527250 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature