目的:STK3在维持细胞稳态方面具有核心作用,扩散,增长,和凋亡。以前,我们研究了MCF-7乳腺癌细胞中STK3/MST2与雌激素受体之间的功能联系。为了扩大调查,这项研究使用公开数据评估了STK3在乳腺癌固有亚型中的高表达和相关基因.
方法:使用描述性和多变量分析来分析临床病理特征与STK3高表达之间的关系。
结果:STK3在乳腺癌中的表达增加与更高的病理分期显着相关,在乳腺癌的内在亚型中观察到不同的表达水平。Kaplan-Meier分析显示,与STK3低表达的乳腺癌患者相比,高表达STK3的乳腺癌患者生存率较低(p<0.05)。多变量分析揭示了STK3表达与IDC患者生存率之间的强相关性。显示较低表达的风险比。在TCGA数据集中,肿瘤死亡患者的风险比为0.56(95%CI0.34-0.94,p=0.029),所有死亡患者为0.62(95%CI0.42-0.92,p=0.017)。此外,在METABRIC数据集中,肿瘤死亡患者的风险比为0.76(95%CI0.64-0.91,p=0.003).根据GSEA结果,基于统计学显著性(FDR<0.25和p<0.05)选择7个基因集。与STK3相关的加权和模型(WSM)衍生的前5%基因在基底中也具有较高的表达,而在腔A中具有较低的表达。
结论:通过引入一种结合了GSEA和WSM的新型生物信息学方法,该研究成功确定了与STK3高表达相关的前5%基因。
OBJECTIVE: 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 significantly associated with higher pathological cancer stages, and a different 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 significance (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.
CONCLUSIONS: By introducing a novel bioinformatics approach that combines GSEA and WSM, the study successfully identified the top 5% of genes associated with higher expression of STK3.