关键词: EZR VIL2 breast cancer ezrin

Mesh : Humans Female Breast Neoplasms / pathology Retrospective Studies Biomarkers, Tumor / genetics metabolism Cytoskeletal Proteins / genetics metabolism Prognosis Receptors, Progesterone Receptor, ErbB-2 / genetics metabolism

来  源:   DOI:10.1002/cam4.5802   PDF(Pubmed)

Abstract:
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.
摘要:
背景:细胞骨架蛋白ezrin在许多癌症类型中上调,并与患者预后不良密切相关。虽然以前已经评估了ezrin在乳腺癌中的临床和预后价值,迄今为止,大多数研究都是在较小的队列中进行的(少于500例),或者集中在特定的疾病特征上。目前的研究是使用诺丁汉(n=1094)和METABRIC(n=1980)队列在早期乳腺癌患者中在蛋白质和mRNA水平上评估ezrin的最大研究。分别。
结果:ezrin的高表达与较大的肿瘤大小显着相关(p=0.027),肿瘤分级较高(p<0.001),诺丁汉预后指数组(p=0.011)和HER2阳性状态(p=0.001)较差。高ezrin表达与乳腺癌患者的不良生存率显着相关(p<0.001),并且在多变量Cox回归分析中仍然与生存率相关(p=0.018,风险比(HR)=1.343,95%置信区间(CI)=1.051-1.716)。高ezrin表达与肿瘤被归类为受体(雌激素受体(ER),孕激素受体(PgR)或HER2)阳性(p<0.001)与被归类为三阴性乳腺癌(p=0.889)相比。METABRIC队列中ezrinmRNA(VIL2)的高表达也与乳腺癌患者的不良生存率显着相关(p<0.001)。
结论:回顾性分析显示ezrin是一个独立的预后指标,在受体阳性的患者中具有与缩短生存期相关的较高表达(ER,PgR或HER2)患者。Ezrin表达与更具侵袭性的疾病相关,可能作为早期乳腺癌患者预后的生物标志物具有临床应用价值。
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