STK3 higher expression association with clinical characteristics in intrinsic subtypes of breast cancer invasive ductal carcinoma patients

Purpose: STK3 has a central role in maintaining cell homeostasis, proliferation, growth, and apoptosis. Previously, we investigated the functional link between STK3/MST2, and estrogen receptor in MCF-7 breast cancer cells. To expand the investigation, this study evaluated STK3’s higher expression and associated genes in breast cancer intrinsic subtypes using publicly available data.

Methods: The relationship between clinical pathologic features and STK3 high expression was analyzed using descriptive and multivariate analysis.

Results: Increased STK3 expression in breast cancer was signifcantly associated with higher pathological cancer stages, and a diferent expression level was observed in the intrinsic subtypes of breast cancer. Kaplan–Meier analysis showed that breast cancer with high STK3 had a lower survival rate in IDC patients than that with low STK3 expression (p<0.05). The multivariate analysis unveiled a strong correlation between STK3 expression and the survival rate among IDC patients, demonstrating hazard ratios for lower expression. In the TCGA dataset, the hazard ratio was 0.56 (95% CI 0.34–0.94, p=0.029) for patients deceased with tumor, and 0.62 (95% CI 0.42–0.92, p=0.017) for all deceased patients. Additionally, in the
METABRIC dataset, the hazard ratio was 0.76 (95% CI 0.64–0.91, p=0.003) for those deceased with tumor. From GSEA outcomes 7 gene sets were selected based on statistical signifcance (FDR<0.25 and p<0.05). Weighted Sum model (WSM) derived top 5% genes also have higher expression in basal and lower in luminal A in association with STK3.

Conclusion: By introducing a novel bioinformatics approach that combines GSEA and WSM, the study successfully identifed the top 5% of genes associated with higher expression of STK3.