Nottingham Breast Cancer Research Centre, Biodiscovery Institute, University of Nottingham, School of Medicine, Nottingham, UK.
Division of Cancer Biology and Genetics, Queen's Cancer Research Institute, Queen's University, Kingston, Ontario, Canada.
Cancer Med. 2023 May;12(9):10908-10916. doi: 10.1002/cam4.5802. Epub 2023 Mar 20.
The cytoskeletal protein ezrin is upregulated in many cancer types and is strongly associated with poor patient outcome. While the clinical and prognostic value of ezrin has been previously evaluated in breast cancer, most studies to date have been conducted in smaller cohorts (less than 500 cases) or have focused on specific disease characteristics. The current study is the largest of its kind to evaluate ezrin both at the protein and mRNA levels in early-stage breast cancer patients using the Nottingham (n = 1094) and METABRIC (n = 1980) cohorts, respectively.
High expression of ezrin was significantly associated with larger tumour size (p = 0.027), higher tumour grade (p < 0.001), worse Nottingham Prognostic Index prognostic group (p = 0.011) and HER2-positive status (p = 0.001). High ezrin expression was significantly associated with adverse survival of breast cancer patients (p < 0.001) and remained associated with survival in multivariate Cox-regression analysis (p = 0.018, hazard ratio (HR) = 1.343, 95% confidence interval (CI) = 1.051-1.716) when potentially confounding factors were included. High ezrin expression was significantly associated with adverse survival of patients whose tumours were categorised as receptor (oestrogen receptor (ER), progesterone receptor (PgR) or HER2) positive (p < 0.001) in comparison to those categorised as triple-negative breast cancer (p = 0.889). High expression of ezrin mRNA (VIL2) in the METABRIC cohort was also significantly associated with adverse survival of breast cancer patients (p < 0.001).
Retrospective analyses show that ezrin is an independent prognostic marker, with higher expression associated with shortened survival in receptor-positive (ER, PgR or HER2) patients. Ezrin expression is associated with more aggressive disease and may have clinical utility as a biomarker of patient prognosis in early-stage breast cancer.
细胞骨架蛋白 ezrin 在许多癌症类型中上调，与患者预后不良密切相关。虽然 ezrin 的临床和预后价值已在乳腺癌中得到评估，但迄今为止的大多数研究都是在较小的队列（少于 500 例）中进行的，或者集中在特定的疾病特征上。本研究是迄今为止使用诺丁汉（n=1094）和 METABRIC（n=1980）队列分别在早期乳腺癌患者中评估 ezrin 蛋白和 mRNA 水平的最大研究。
ezrin 高表达与肿瘤较大（p=0.027）、肿瘤分级较高（p<0.001）、诺丁汉预后指数预后组较差（p=0.011）和 HER2 阳性状态（p=0.001）显著相关。ezrin 高表达与乳腺癌患者不良生存显著相关（p<0.001），并在多变量 Cox 回归分析中仍然与生存相关（p=0.018，危险比（HR）=1.343，95%置信区间（CI）=1.051-1.716），当纳入潜在混杂因素时。在肿瘤被归类为受体（雌激素受体（ER）、孕激素受体（PgR）或 HER2）阳性的患者中，ezrin 高表达与三阴性乳腺癌患者（p=0.889）相比，与不良生存显著相关（p<0.001）。在 METABRIC 队列中，ezrin mRNA（VIL2）的高表达也与乳腺癌患者的不良生存显著相关（p<0.001）。
回顾性分析表明，ezrin 是一个独立的预后标志物，高表达与受体阳性（ER、PgR 或 HER2）患者的生存缩短相关。ezrin 表达与更具侵袭性的疾病相关，可能具有作为早期乳腺癌患者预后生物标志物的临床应用价值。
