Giaginis Constantinos, Sampani Anastasia, Kotta-Loizou Iolly, Giannopoulou Ioanna, Danas Eugene, Politi Ekaterini, Tsourouflis Gerasimos, Kouraklis Gregorios, Patsouris Efstratios, Keramopoulos Antonios, Nakopoulou Lydia, Theocharis Stamatios
First Department of Pathology, Medical School, University of Athens, Athens, Greece.
Department of Food Science and Nutrition, University of the Aegean, Myrina, Lemnos, Greece.
Pathol Oncol Res. 2018 Jul;24(3):631-640. doi: 10.1007/s12253-017-0288-1. Epub 2017 Aug 14.
Hu-antigen R (HuR), a RNA-binding protein, is considered to play a crucial role in tumor development and progression by stabilizing or regulating a group of cellular mRNAs of cancer-related genes, such as cyclooxygenase-2 (COX-2). The present study aimed to evaluate the clinical significance of HuR and COX-2 expression in invasive breast carcinoma. HuR and COX-2 protein expression was assessed immunohistochemically on paraffin-embedded breast cancer tissue sections obtained from 121 patients and was statistically analyzed with clinicopathological parameters, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), as well as with tumor cells' proliferative capacity and overall and disease-free patients' survival. High HuR expression was positively associated with larger tumor size and advanced disease stage (p = 0.0234 and p = 0.0361, respectively), being more frequently observed in ER negative cases (p = 0.0208). High COX-2 expression was negatively associated with histological (p < 0.0001) and nuclear (p = 0.0033) grade and tumor cells' proliferative rate (p = 0.0015), being more frequently observed in luminal-A compared to other molecular subtypes (p = 0.0221). High HuR expression was associated with poor overall and disease-free patients' survival at both univariate (log-rank test, p = 0.0092 and p = 0.0004, respectively) and multivariate (Cox-regression analysis, p = 0.0223 and p = 0.0004, respectively) level. On the other hand, high COX-2 expression was associated with favorable overall and disease-free patients' survival merely at univariate level (log-rank test, p = 0.0389 and p = 0.0154, respectively). HuR expression was not associated with COX-2 expression (Spearman R = 0.1489, p = 0.1032). The present data support evidence that HuR is associated with tumor aggressiveness and poor prognosis in breast carcinoma, reinforcing its potential as promising therapeutic target in this type of neoplasia.
Hu抗原R（HuR）是一种RNA结合蛋白，被认为通过稳定或调节一组癌症相关基因的细胞mRNA，如环氧合酶-2（COX-2），在肿瘤发生和发展中起关键作用。本研究旨在评估HuR和COX-2表达在浸润性乳腺癌中的临床意义。采用免疫组织化学方法对121例患者石蜡包埋的乳腺癌组织切片进行HuR和COX-2蛋白表达评估，并与临床病理参数、雌激素受体（ER）、孕激素受体（PR）和人表皮生长因子受体2（HER2）以及肿瘤细胞增殖能力和患者总生存期及无病生存期进行统计学分析。HuR高表达与肿瘤较大尺寸和疾病晚期呈正相关（分别为p = 0.0234和p = 0.0361），在ER阴性病例中更常见（p = 0.0208）。COX-2高表达与组织学分级（p < 0.0001）、核分级（p = 0.0033）和肿瘤细胞增殖率（p = 0.0015）呈负相关，与其他分子亚型相比，在腔面A型中更常见（p = 0.0221）。HuR高表达在单因素（对数秩检验，分别为p = 0.0092和p = 0.0004）和多因素（Cox回归分析，分别为p = 0.0223和p = 0.0004）水平上均与患者总生存期和无病生存期较差相关。另一方面，COX-2高表达仅在单因素水平上与患者总生存期和无病生存期良好相关（对数秩检验，分别为p = 0.0389和p = 0.0154）。HuR表达与COX-2表达无关（Spearman相关系数R = 0.1489，p = 0.1032）。本研究数据支持HuR与乳腺癌肿瘤侵袭性和不良预后相关的证据，强化了其作为这种肿瘤类型有前景的治疗靶点的潜力。
