Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, UK.
Department of Pathology, Faculty of Medicine, Menoufia University, Shebin El Kom, Egypt.
Histopathology. 2023 Sep;83(3):414-425. doi: 10.1111/his.14960. Epub 2023 May 24.
Polo-like kinase-1 (PLK1) plays a crucial role in cell cycle progression, and it is considered a potential therapeutic target in many cancers. Although the role of PLK1 is well established in triple-negative breast cancer (TNBC) as an oncogene, its role in luminal BC is still controversial. In this study, we aimed to evaluate the prognostic and predictive role of PLK1 in BC and its molecular subtypes.
A large BC cohort (n = 1208) were immunohistochemically stained for PLK1. The association with clinicopathological, molecular subtypes, and survival data was analysed. PLK1 mRNA was evaluated in the publicly available datasets (n = 6774), including The Cancer Genome Atlas and the Kaplan-Meier Plotter tool.
20% of the study cohort showed high cytoplasmic PLK1 expression. High PLK1 expression was significantly associated with a better outcome in the whole cohort, luminal BC. In contrast, high PLK1 expression was associated with a poor outcome in TNBC. Multivariate analyses indicated that high PLK1 expression is independently associated with longer survival in luminal BC, and in poorer prognosis in TNBC. At the mRNA levels, PLK1 expression was associated with short survival in TNBC consistent with the protein expression. However, in luminal BC, its prognostic value significantly varies between cohorts.
The prognostic role of PLK1 in BC is molecular subtype-dependent. As PLK1 inhibitors are introduced to clinical trials for several cancer types, our study supports evaluation of the pharmacological inhibition of PLK1 as an attractive therapeutic target in TNBC. However, in luminal BC, PLK1 prognostic role remains controversial.
丝氨酸/苏氨酸激酶 Polo 样激酶-1（PLK1）在细胞周期进展中发挥着关键作用，它被认为是许多癌症的潜在治疗靶点。尽管 PLK1 在三阴性乳腺癌（TNBC）中作为致癌基因的作用已得到充分证实，但它在管腔 BC 中的作用仍存在争议。在这项研究中，我们旨在评估 PLK1 在 BC 及其分子亚型中的预后和预测作用。
对一个大型 BC 队列（n=1208）进行了 PLK1 的免疫组织化学染色。分析了与临床病理、分子亚型和生存数据的关联。在包括癌症基因组图谱和 Kaplan-Meier Plotter 工具在内的公共可用数据集（n=6774）中评估了 PLK1 mRNA。
研究队列中有 20%的患者表现出高细胞质 PLK1 表达。高 PLK1 表达与整个队列、管腔 BC 的更好结局显著相关。相反，高 PLK1 表达与 TNBC 的不良结局相关。多变量分析表明，高 PLK1 表达与管腔 BC 的生存时间延长独立相关，与 TNBC 的预后不良相关。在 mRNA 水平上，PLK1 表达与 TNBC 的短生存时间相关，与蛋白表达一致。然而，在管腔 BC 中，其预后价值在不同队列之间存在显著差异。
PLK1 在 BC 中的预后作用依赖于分子亚型。由于 PLK1 抑制剂已被引入到几种癌症类型的临床试验中，我们的研究支持评估 PLK1 的药理学抑制作为 TNBC 有吸引力的治疗靶点。然而，在管腔 BC 中，PLK1 的预后作用仍存在争议。
