Children’s Nutrition Research Center Staff Publications

Language

English

Publication Date

2-17-2023

Journal

Nature Communications

DOI

10.1038/s41467-023-36558-1

PMID

36807354

PMCID

PMC9938262

PubMedCentral® Posted Date

2-17-2023

PubMedCentral® Full Text Version

Post-print

Abstract

Intratumoral heterogeneity (ITH) has been linked to decreased efficacy of clinical treatments. However, although genomic ITH has been characterized in genetic, transcriptomic and epigenetic alterations are hallmarks of esophageal squamous cell carcinoma (ESCC), the extent to which these are heterogeneous in ESCC has not been explored in a unified framework. Further, the extent to which tumor-infiltrated T lymphocytes are directed against cancer cells, but how the immune infiltration acts as a selective force to shape the clonal evolution of ESCC is unclear. In this study, we perform multi-omic sequencing on 186 samples from 36 primary ESCC patients. Through multi-omics analyses, it is discovered that genomic, epigenomic, and transcriptomic ITH are underpinned by ongoing chromosomal instability. Based on the RNA-seq data, we observe diverse levels of immune infiltrate across different tumor sites from the same tumor. We reveal genetic mechanisms of neoantigen evasion under distinct selection pressure from the diverse immune microenvironment. Overall, our work offers an avenue of dissecting the complex contribution of the multi-omics level to the ITH in ESCC and thereby enhances the development of clinical therapy.

Keywords

Humans, Esophageal Squamous Cell Carcinoma, Esophageal Neoplasms, Multiomics, Transcriptome, Gene Expression Profiling, Tumor Microenvironment, Cancer genomics, Oesophageal cancer, Cancer epigenetics, Tumour heterogeneity, Tumour immunology

Published Open-Access

yes

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