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Identification and Validation of a Necroptosis-Related Prognostic Model in Tumor Recurrence and Tumor Immune Microenvironment in Breast Cancer Management

  • 0Department of General Surgery, the Second Xiangya Hospital of Central South University, Changsha, Hunan, People's Republic of China.
Journal of Inflammation Research +

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July 31, 2024

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July 31, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Necroptosis influences breast cancer immunity and recurrence. Targeting necroptosis with specific gene sets can improve immunotherapy response and predict patient prognosis, aiding personalized breast cancer treatment.

Area Of Science

  • Oncology
  • Immunology
  • Molecular Biology

Background

  • Breast cancer is a leading cause of cancer death in women.
  • Necroptosis, a cell death pathway, impacts anti-tumor immunity in solid tumors like breast cancer.
  • The specific role of necroptosis in breast cancer recurrence is not well understood.

Purpose Of The Study

  • To investigate the role of necroptosis in breast cancer immunity and recurrence.
  • To identify necroptotic signatures for patient stratification and prognosis prediction.
  • To explore necroptosis-targeting strategies for enhancing immunotherapy.

Main Methods

  • Utilized gene expression and clinical data from GEO and TCGA databases.
  • Employed unsupervised clustering and LASSO-COX regression for patient stratification.
  • Conducted GO, KEGG, GSVA, ESTIMATE, and ROC analyses to assess necroptotic signatures.
  • Performed in vitro and in vivo experiments to validate findings.

Main Results

  • Identified two prognostic models stratifying patients based on necroptotic profiles.
  • Found a correlation between low-risk groups, specific necroptotic immune signatures, and elevated immune cell/pathway activity.
  • Observed altered immune checkpoint patterns (e.g., increased TIM-3, LAGLS9) in the low-risk group.
  • Demonstrated that manipulating necroptotic genes sensitizes tumors to anti-TIM-3 and anti-PD-1 immunotherapy.

Conclusions

  • Developed strategies to stratify breast cancer patients using necroptotic profiles, linking them to distinct immune microenvironments and recurrence prognoses.
  • Identified a necroptotic gene set (TLR3, RIPK3, NLRP3, CASP1, ALDH2, EZH2) as a biomarker for predicting immunotherapy response and recurrence.
  • Targeting necroptosis offers potential for novel breast cancer treatments and personalized medicine.

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