Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham, UK.
Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma, Japan.
Breast Cancer Res Treat. 2019 Apr;174(2):387-399. doi: 10.1007/s10549-018-05085-9. Epub 2018 Dec 15.
CD133/ prominin 1 is a cancer stem cell marker associated with cancer progression and patient outcome in a variety of solid tumours, but its role in invasive breast cancer (BC) remains obscure. The current study aims to assess the prognostic value of CD133 expression in early invasive BC.
CD133 mRNA was assessed in the METABRIC cohort and at the proteomic level using immunohistochemistry utilising a large well-characterised BC cohort. Association with clinicopathological characteristics, expression of other stem cell markers and patient outcome were evaluated.
High expression of CD133 either in mRNA or protein levels was associated with characteristics of poor prognosis including high tumour grade, larger tumour size, high Nottingham Prognostic Index, HER2 positivity and hormonal receptor negativity (all; p < 0.001). High CD133 expression was positively associated with proliferation biomarkers including p16, Cyclin E and Ki67 (p < 0.01). Tumours expressing CD133 showed higher expression of other stem cell markers including CD24, CD44, SOX10, ALDHA3 and ITGA6. High expression of CD133 protein was associated with shorter BC-specific survival (p = 0.026). Multivariate analysis revealed that CD133 protein expression was an independent risk factor for shorter BC-specific survival (p = 0.038).
This study provides evidence for the prognostic value of CD133 in invasive BC. A strong positive association of BC stem cell markers is observed at the protein level. Further studies to assess the value of stem cell markers individually or in combination in BC is warranted.
CD133/ prominin 1 是一种与多种实体瘤的癌症进展和患者预后相关的癌症干细胞标志物，但它在浸润性乳腺癌（BC）中的作用仍不清楚。本研究旨在评估 CD133 表达在早期浸润性 BC 中的预后价值。
在 METABRIC 队列中评估 CD133 mRNA，并利用免疫组织化学技术在大型经过充分特征描述的 BC 队列中评估其蛋白质水平。评估其与临床病理特征、其他干细胞标志物的表达和患者预后的关系。
无论是在 mRNA 还是蛋白水平上，CD133 的高表达均与预后不良的特征相关，包括高肿瘤分级、更大的肿瘤大小、高 Nottingham 预后指数、HER2 阳性和激素受体阴性（均为 p<0.001）。CD133 的高表达与增殖生物标志物包括 p16、Cyclin E 和 Ki67 呈正相关（p<0.01）。表达 CD133 的肿瘤表现出其他干细胞标志物包括 CD24、CD44、SOX10、ALDHA3 和 ITGA6 的高表达。CD133 蛋白的高表达与较短的 BC 特异性生存相关（p=0.026）。多变量分析显示 CD133 蛋白表达是较短的 BC 特异性生存的独立危险因素（p=0.038）。
本研究为 CD133 在浸润性 BC 中的预后价值提供了证据。在蛋白质水平上观察到 BC 干细胞标志物之间存在强烈的正相关性。进一步研究评估 BC 中干细胞标志物单独或联合使用的价值是必要的。
