Clinical evidence for a role of E2F1-induced replication stress in modulating tumor mutational burden and immune microenvironment

Ke Tan, Yizhe Song, Min Xu, Zhongsheng You

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

DNA replication stress (RS) is frequently induced by oncogene activation and is believed to promote tumorigenesis. However, clinical evidence for the role of oncogene-induced RS in tumorigenesis remains scarce, and the mechanisms by which RS promotes cancer development remain incompletely understood. By performing a series of bioinformatic analyses on the oncogene E2F1, other RS-inducing factors, and replication fork processing factors in TCGA cancer database using previously established tools, we show that hyperactivity of E2F1 likely promotes the expression of several of these factors in virtually all types of cancer to induce RS and cytosolic self-DNA production. In addition, the expression of these factors positively correlates with that of ATR and Chk1 that govern the cellular response to RS, the tumor mutational load, and tumor infiltration of immune-suppressive CD4+Th2 cells and myeloid-derived suppressor cells (MDSCs). Consistently, high expression of these factors is associated with poor patient survival. Our study provides new insights into the role of E2F1-induced RS in tumorigenesis and suggests therapeutic approaches for E2F1-overexpressing cancers by targeting genomic instability, cytosolic self-DNA and the tumor immune microenvironment.

Original languageEnglish
Article number103531
JournalDNA Repair
Volume129
DOIs
StatePublished - Sep 2023

Keywords

  • Cytosolic self-DNA
  • E2F1
  • Replication stress
  • Tumor immune microenvironment
  • Tumor mutational burden

Fingerprint

Dive into the research topics of 'Clinical evidence for a role of E2F1-induced replication stress in modulating tumor mutational burden and immune microenvironment'. Together they form a unique fingerprint.

Cite this