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肌氨酸病毒抗性蛋白 1(MX1)是浸润性乳腺癌不良预后的独立预测因子。

Myxovirus resistance 1 (MX1) is an independent predictor of poor outcome in invasive breast cancer.

机构信息

Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham, NG7 2RD, UK.

Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Taif University, Taif, Saudi Arabia.

出版信息

Breast Cancer Res Treat. 2020 Jun;181(3):541-551. doi: 10.1007/s10549-020-05646-x. Epub 2020 Apr 29.

Abstract

BACKGROUND

Breast cancer (BC) is a disease with variable morphology, clinical behaviour and response to therapy. Identifying factors associated with the progression of early-stage BC can help understand the risk of metastasis and guide treatment decisions. Myxovirus resistance 1 (MX1), which is involved in the cellular antiviral mechanism, plays a role in some solid tumours; however, its role in invasive BC remains unknown. In this study, we aimed to explore the clinicopathological and prognostic significance of MX1 in BC.

METHODS

MX1 was assessed at the protein level using tissue microarrays from a large well-annotated BC cohort (n = 845). The expression of MX1 mRNA was assessed at the transcriptomic level using the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC; n = 1980) and validated using three publicly available cohorts on Breast Cancer Gene-Expression Miner (bc-GenExMiner version 4.4). The associations between MX1 expression and clinicopathological factors, and outcome were evaluated.

RESULTS

High MX1 protein expression was associated with features of aggressiveness, including large tumour size, high tumour grade, high Nottingham prognostic index scores, hormone receptor negativity and high Ki67 expression. High MX1 expression showed an association with poor patient outcome and it was an independent predictor of short BC-specific survival (p = 0.028; HR = 1.5; 95% CI = 1.0-2.2). Consistent with the protein results, high MX1 mRNA levels showed an association with features of aggressive behaviour and with shorter survival.

CONCLUSION

This study identified MX1 as an independent predictor of poor outcome in patients with BC. Further functional studies are needed to investigate the biological role of MX1 in BC and its potential value as a therapeutic target.

摘要

背景

乳腺癌(BC)是一种形态学、临床行为和治疗反应均具有多变性的疾病。识别与早期 BC 进展相关的因素有助于了解转移风险,并指导治疗决策。参与细胞抗病毒机制的肌炎病毒抗性蛋白 1(MX1)在一些实体肿瘤中发挥作用;然而,其在浸润性 BC 中的作用尚不清楚。本研究旨在探讨 MX1 在 BC 中的临床病理和预后意义。

方法

使用大型注释良好的 BC 队列(n=845)的组织微阵列评估 MX1 的蛋白水平。使用乳腺癌国际联合会的分子分类(METABRIC;n=1980)评估 MX1 mRNA 的转录组水平,并使用三个公开的乳腺癌基因表达 Miner(bc-GenExMiner 版本 4.4)进行验证。评估了 MX1 表达与临床病理因素和结局之间的关联。

结果

高 MX1 蛋白表达与侵袭性特征相关,包括肿瘤较大、肿瘤分级较高、诺丁汉预后指数评分较高、激素受体阴性和 Ki67 表达较高。高 MX1 表达与患者预后不良相关,是 BC 特异性生存时间短的独立预测因子(p=0.028;HR=1.5;95%CI=1.0-2.2)。与蛋白结果一致,高 MX1 mRNA 水平与侵袭性行为特征和较短的生存时间相关。

结论

本研究将 MX1 确定为 BC 患者不良结局的独立预测因子。需要进一步的功能研究来探讨 MX1 在 BC 中的生物学作用及其作为治疗靶点的潜在价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1426/7220876/56cd17a3e779/10549_2020_5646_Fig1_HTML.jpg

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