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DDIT3 is associated with breast cancer prognosis and immune microenvironment: an integrative bioinformatic and immunohistochemical analysis

  • 0Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China.
Journal of Cancer +

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June 24, 2024

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June 24, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

DNA damage-inducible transcript 3 (DDIT3) impacts breast cancer progression and immune interactions. A novel six-gene signature linked to DDIT3 predicts poor prognosis and identifies patients sensitive to immunotherapy.

Area Of Science

  • Oncology
  • Molecular Biology
  • Immunology

Background

  • DNA damage-inducible transcript 3 (DDIT3) is a transcription factor involved in apoptosis and stress response, with known roles in cancer biology.
  • Its specific role in breast cancer progression and its interaction with the tumor immune microenvironment remain incompletely understood.

Purpose Of The Study

  • To investigate the role of DDIT3 in breast cancer progression using a multi-omics approach.
  • To establish a correlation between DDIT3 expression and patient prognosis.
  • To explore the relationship between DDIT3 and the breast cancer immune microenvironment.

Main Methods

  • Utilized a multi-omics integration strategy including bulk RNA sequencing, single-cell sequencing, spatial transcriptomics, and immunohistochemistry.
  • Developed a prognostic gene signature associated with DDIT3.
  • Analyzed immune cell infiltration and signaling pathways in relation to DDIT3 and the prognostic signature.

Main Results

  • Identified a six-gene prognostic signature (including unc-93 homolog B1, TLR signaling regulator, anti-Mullerian hormone, DCTP pyrophosphatase 1, mitochondrial ribosomal protein L36, nuclear factor erythroid 2, and Rho GTPase activating protein 39) significantly associated with DDIT3 and poor breast cancer prognosis.
  • High-risk patients exhibited increased regulatory T cell and M2-like macrophage infiltration, alongside fibroblast growth factor (FGF)/FGF receptor signaling activation.
  • Spatial analysis revealed DDIT3's correlation with immune cell infiltration within the tumor microenvironment.
  • High-risk group showed enhanced sensitivity to immunotherapy.

Conclusions

  • DDIT3 plays a significant role in breast cancer progression and influences the tumor immune microenvironment.
  • The identified DDIT3-related prognostic signature can stratify patients and predict outcomes.
  • Findings suggest novel therapeutic strategies and personalized treatment approaches for breast cancer based on DDIT3 status and immune microenvironment interactions.

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