Impaired TGF-β signaling via AHNAK family mutations elicits an esophageal cancer subtype with sensitivities to genotoxic therapy and immunotherapy.

ABSTRACT:

Background

Genome instability (GI) is a hallmark of esophageal squamous cell carcinoma (ESCC) while factors affecting GI remain unclear.

Methods

Here, we aimed to characterize genomic events representing specific mechanisms of GI based on 201 ESCC samples and validated our findings at the patient, single-cell and cancer cell-line levels, including a newly generated multi-omics dataset of the trial NCT04006041.

Results

A two-gene (AHNAK and AHNAK2) mutation signature was identified to define the "AHNAK1/2-mutant" cancer subtype. Single-cell-assisted multi-omics analysis showed that this subtype had a higher neoantigen load, active antigen presentation, and proficient CD8 + T cell infiltrations, which were validated at pan-cancer levels. Mechanistically, AHNAK1/2-mutant

SUBMITTER: Mai Z 

PROVIDER: S-EPMC11377381 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature