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

Abstract

The cyclin-dependent kinase inhibitor 1B (CDKN1B) gene, which encodes the p27Kip1 protein, is important in regulating the cell cycle process and cell proliferation. Its role in breast cancer prognosis is controversial. We evaluated the significance and predictive role of CDKN1B expression in breast cancer prognosis. We investigated the clinicopathologic factors, survival rates, immune cells, gene sets, and prognostic models according to CDKN1B expression in 3794 breast cancer patients. We performed gene set enrichment analysis (GSEA), in silico cytometry, pathway network analyses, gradient boosting machine (GBM) learning, and in vitro drug screening. High CDKN1B expression levels in breast cancer correlated with high lymphocyte infiltration signature scores and increased CD8+ T cells, both of which were associated with improved prognosis in breast cancer. which were associated with a better prognosis. CDKN1B expression was associated with gene sets for the upregulation of T-cell receptor signaling pathways and downregulation of CD8+ T cells. Pathway network analysis revealed a direct link between CDKN1B and the pathway involved in the positive regulation of the protein catabolic process pathway. In addition, an indirect link was identified between CDKN1B and the T-cell receptor signaling pathway. In in vitro drug screening, BMS-345541 demonstrated efficacy as a therapeutic targeting of CDKN1B, effectively impeding the growth of breast cancer cells characterized by low CDKN1B expression. The inclusion of CDKN1B expression in GBM models increased the accuracy of survival predictions. CDKN1B expression plays a significant role in breast cancer progression, implying that targeting CDKN1B might be a promising strategy for treating breast cancer.