JMJD8 overexpression in breast cancer: implications for diagnosis, prognosis, and immune microenvironment

Chenlei Zhu1, Tianyi Xi1, Guorong Yang1

  • 1Department of General Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China.

Frontiers in Oncology
|August 5, 2025
PubMed
Abstract

Insights

JMJD8 is elevated in breast cancer, worsening prognosis and immune suppression. Knocking out JMJD8 enhances anti-tumor immunity and inhibits cancer cell proliferation, suggesting JMJD8 as a prognostic biomarker.

Area of Science:

  • Oncology
  • Immunology
  • Biomarker Discovery

Background:

  • Breast cancer diagnosis and therapy remain challenging due to late detection and limited treatment options.
  • The role of JMJD8 in breast cancer and its impact on the tumor microenvironment are not well understood.
  • Systematic evaluation of potential breast cancer biomarkers is needed.

Purpose of the Study:

  • To investigate the association between JMJD8 expression and breast cancer prognosis.
  • To explore the relationship between JMJD8 and the immune infiltration microenvironment in breast cancer.
  • To evaluate JMJD8 as a potential prognostic biomarker for breast cancer.

Main Methods:

  • Utilized The Cancer Genome Atlas (TCGA) data for breast cancer (BRCA) patients.
  • Assessed JMJD8 expression correlation with clinical characteristics using Wilcoxon signed-rank test and logistic regression.
  • Analyzed overall survival impact via Kaplan-Meier and Cox regression.
  • Created JMJD8 knockout BRCA cell lines for in vitro and in vivo studies on proliferation and anti-tumor immunity.

Main Results:

  • JMJD8 expression is significantly elevated in BRCA tissues compared to normal tissues.
  • High JMJD8 expression correlates with advanced pathological stages and predicts poor overall survival.
  • JMJD8 knockout enhances anti-tumor immunity by activating the cGAS-STING pathway, promoting dendritic cell maturation, and inhibiting BRCA cell proliferation.
  • JMJD8 expression positively correlates with M2 macrophage infiltration, suggesting a role in creating an immunosuppressive tumor microenvironment.

Conclusions:

  • Elevated JMJD8 expression in breast cancer is linked to disease progression and altered immune cell infiltration.
  • JMJD8 may serve as a prognostic biomarker, indicating immunosuppressive tumor characteristics.
  • Targeting JMJD8 could lead to novel therapeutic strategies for breast cancer management.

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