Low CDKN1B Expression Associated with Reduced CD8+ T Lymphocytes Predicts Poor Outcome in Breast Cancer in a Machine...

Area of Science:

• Oncology
• Molecular Biology
• Immunology

Background:

• The cyclin-dependent kinase inhibitor 1B (CDKN1B) gene, encoding p27Kip1, regulates cell cycle and proliferation.
• Its prognostic significance in breast cancer remains debated.
• Understanding CDKN1B's role is crucial for developing targeted breast cancer therapies.

Purpose of the Study:

• To evaluate the prognostic and predictive value of CDKN1B expression in breast cancer.
• To investigate associations between CDKN1B expression and clinicopathologic factors, survival, immune infiltration, and gene expression profiles.
• To explore CDKN1B's role in breast cancer progression and therapeutic targeting.

Main Methods:

• Analysis of 3794 breast cancer patient data.
• Gene Set Enrichment Analysis (GSEA).
• In silico cytometry, pathway network analyses, and gradient boosting machine (GBM) learning.
• In vitro drug screening.

Main Results:

• High CDKN1B expression correlated with increased lymphocyte infiltration and CD8+ T cells, associated with improved breast cancer prognosis.
• CDKN1B expression linked to T-cell receptor signaling pathways and protein catabolic processes.
• Drug screening identified BMS-345541 as effective against low CDKN1B breast cancer cells.
• Incorporating CDKN1B into GBM models improved survival prediction accuracy.

Conclusions:

• CDKN1B expression is a significant prognostic factor in breast cancer.
• CDKN1B influences immune cell infiltration and T-cell signaling.
• Targeting CDKN1B presents a potential therapeutic strategy for breast cancer treatment.