Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Department of Pathology, Odense University Hospital, Odense, Denmark.
Int J Cancer. 2015 Nov 1;137(9):2093-103. doi: 10.1002/ijc.29582. Epub 2015 May 21.
Triple-negative breast cancer (TNBC) represents a heterogeneous subgroup with generally poor outcome and lack of an effective targeted therapy. Prognostic or predictive biomarkers to guide treatment decisions for this group of patients are needed. To evaluate the potential of S100A14 protein as a novel biomarker in TNBC, the protein expression of S100A14 was correlated with clinical outcomes in a Pilot Sample set and a Danish cohort of predominantly TNBC patients. Kaplan-Meier analysis identified a prognostic impact of S100A14 on disease-free survival and overall survival, showing that tumors with high S100A14 protein expression levels were significantly correlated with poor outcome in TNBC patients (p = 0.017; p = 0.038), particularly those in the basal-like subgroup (p = 0.006; p = 0.037). Importantly, TNBC patients with high S100A14 expression, but tumor-negative axillary lymph nodes (N-), had equally poor outcomes as those with tumor-positive axillary lymph nodes (N+), while TNBC/N- patients with low S100A14 expression had a significantly better disease free survival (p = 0.013). Multivariate analysis revealed that S100A14 is an independent prognostic factor for TNBC patients (p = 0.024; p = 0.05). At the cellular level, S100A14 was found to be expressed in epithelial-like, but not in mesenchymal-like, TNBC cells in vitro. S100A14 is an independent prognostic factor in TNBC and a novel potential therapeutic target in TNBC.
三阴性乳腺癌(TNBC)代表一种异质性亚组,通常预后较差,缺乏有效的靶向治疗。需要预测或预测生物标志物来指导这组患者的治疗决策。为了评估 S100A14 蛋白作为 TNBC 新型生物标志物的潜力,在一个初步样本集和一个主要为 TNBC 患者的丹麦队列中,对 S100A14 的蛋白表达与临床结果进行了相关性分析。Kaplan-Meier 分析确定了 S100A14 对无病生存率和总生存率的预后影响,表明高 S100A14 蛋白表达水平的肿瘤与 TNBC 患者的不良预后显著相关(p = 0.017;p = 0.038),尤其是基底样亚组(p = 0.006;p = 0.037)。重要的是,高 S100A14 表达但腋窝淋巴结阴性(N-)的 TNBC 患者与腋窝淋巴结阳性(N+)的患者的预后同样差,而低 S100A14 表达的 TNBC/N-患者的无病生存率显著更好(p = 0.013)。多变量分析表明,S100A14 是 TNBC 患者的独立预后因素(p = 0.024;p = 0.05)。在细胞水平上,发现 S100A14 在体外表达于上皮样而非间充质样 TNBC 细胞中。S100A14 是 TNBC 的独立预后因素,也是 TNBC 的一种新的潜在治疗靶点。