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NEDD4 expression is associated with breast cancer progression and is predictive of a poor prognosis.
Breast Cancer Research ( IF 6.1 ) Pub Date : 2019-12-19 , DOI: 10.1186/s13058-019-1236-7
Lingfeng Wan 1, 2 , Tao Liu 1, 2 , Zhipeng Hong 2, 3 , You Pan 1 , Steven T Sizemore 2 , Junran Zhang 2 , Zhefu Ma 1, 4
Affiliation  

BACKGROUND A role for neural precursor cell-expressed developmentally downregulated gene 4 (NEDD4) in tumorigenesis has been suggested. However, information is lacking on its role in breast tumor biology. The purpose of this study was to determine the role of NEDD4 in the promotion of the growth and progression of breast cancer (BC) and to evaluate the clinicopathologic and prognostic significance of NEDD4. METHODS The impact of NEDD4 expression in BC cell growth was determined by Cell Counting Kit-8 and colony formation assays. Formalin-fixed paraffin-embedded specimens were collected from 133 adjacent normal tissues (ANTs), 445 BC cases composed of pre-invasive ductal carcinoma in situ (DCIS, n = 37), invasive ductal carcinomas (IDC, n = 408, 226 without and 182 with lymph node metastasis), and 116 invaded lymph nodes. The expression of NEDD4 was analyzed by immunohistochemistry. The association between NEDD4 expression and clinicopathological characteristics was analyzed by chi-square test. Survival was evaluated using the Kaplan-Meier method, and curves were compared using a log-rank test. Univariate and multivariate analyses were performed using the Cox regression method. RESULTS NEDD4 promoted BC growth in vitro. In clinical retrospective studies, 16.5% of ANTs (22/133) demonstrated positive NEDD4 staining. Strikingly, the proportion of cases showing NEDD4-positive staining increased to 51.4% (19/37) in DCIS, 58.4% (132/226) in IDC without lymph node metastasis, and 73.1% (133/182) in BC with lymph node metastasis (BCLNM). In addition, NEDD4-positive staining was associated with clinical parameters, including tumor size (P = 0.030), nodal status (P = 0.001), estrogen receptor status (P = 0.035), and progesterone receptor status (P = 0.023). Moreover, subset analysis in BCLNM revealed that high NEDD4 expression correlated with an elevated risk of relapse (P = 0.0276). Further, NEDD4 expression was an independent prognostic predictor. Lastly, the rates for 10-year overall survival and disease-free survival were significantly lower in patients with positive NEDD4 staining than those in BC patients with negative NEDD4 staining BC (P = 0.0024 and P = 0.0011, respectively). CONCLUSIONS NEDD4 expression is elevated in BC and is associated with BC growth. NEDD4 correlated with clinicopathological parameters and predicts a poor prognosis. Thus, NEDD4 is a potential biomarker of poor prognosis and a potential therapeutic target for BC treatment.

中文翻译:

NEDD4表达与乳腺癌的进展有关,并预示不良预后。

背景技术已经提出了神经前体细胞表达的发育下调基因4(NEDD4)在肿瘤发生中的作用。但是,缺乏有关其在乳腺肿瘤生物学中的作用的信息。这项研究的目的是确定NEDD4在促进乳腺癌(BC)生长和进展中的作用,并评估NEDD4的临床病理和预后意义。方法通过Cell Counting Kit-8和集落形成试验确定NEDD4表达对BC细胞生长的影响。从133个相邻的正常组织(ANTs),445例由浸润前导管原位癌(DCIS,n = 37),浸润性导管癌(IDC,n = 408,226无182例有淋巴结转移),还有116例侵犯了淋巴结。通过免疫组织化学分析NEDD4的表达。通过卡方检验分析NEDD4表达与临床病理特征之间的关联。使用Kaplan-Meier方法评估生存率,并使用对数秩检验比较曲线。使用Cox回归方法进行单变量和多变量分析。结果NEDD4促进了BC的体外生长。在临床回顾性研究中,有16.5%的ANT(22/133)显示NEDD4染色呈阳性。令人惊讶的是,NEDD4阳性染色的病例比例在DCIS中上升至51.4%(19/37),在没有淋巴结转移的IDC中上升为58.4%(132/226),在有淋巴结的BC中上升为73.1%(133/182)转移(BCLNM)。此外,NEDD4阳性染色与临床参数有关,包括肿瘤大小(P = 0.030),淋巴结状态(P = 0)。001),雌激素受体状态(P = 0.035)和孕激素受体状态(P = 0.023)。此外,BCLNM中的子集分析显示,NEDD4高表达与复发风险升高相关(P = 0.0276)。此外,NEDD4表达是独立的预后指标。最后,NEDD4染色阳性的患者10年总生存率和无病生存率显着低于NEDD4染色阴性的BC患者(分别为P = 0.0024和P = 0.0011)。结论NEDD4表达在BC中升高,并与BC的生长有关。NEDD4与临床病理参数相关,并预后不良。因此,NEDD4是预后不良的潜在生物标志物,也是BC治疗的潜在治疗靶标。和孕激素受体状态(P = 0.023)。此外,BCLNM中的子集分析显示,NEDD4高表达与复发风险升高相关(P = 0.0276)。此外,NEDD4表达是独立的预后指标。最后,NEDD4染色阳性的患者10年总生存率和无病生存率显着低于NEDD4染色阴性的BC患者(分别为P = 0.0024和P = 0.0011)。结论NEDD4表达在BC中升高,并与BC的生长有关。NEDD4与临床病理参数相关,并预示不良预后。因此,NEDD4是预后不良的潜在生物标志物,也是BC治疗的潜在治疗靶标。和孕激素受体状态(P = 0.023)。此外,BCLNM中的子集分析显示,NEDD4高表达与复发风险升高相关(P = 0.0276)。此外,NEDD4表达是独立的预后指标。最后,NEDD4染色阳性的患者10年总生存率和无病生存率显着低于NEDD4染色阴性的BC患者(分别为P = 0.0024和P = 0.0011)。结论NEDD4在BC中表达升高,并与BC的生长有关。NEDD4与临床病理参数相关,并预后不良。因此,NEDD4是预后不良的潜在生物标志物,也是BC治疗的潜在治疗靶标。BCLNM中的亚组分析显示,NEDD4高表达与复发风险升高相关(P = 0.0276)。此外,NEDD4表达是独立的预后指标。最后,NEDD4染色阳性的患者10年总生存率和无病生存率显着低于NEDD4染色阴性的BC患者(分别为P = 0.0024和P = 0.0011)。结论NEDD4表达在BC中升高,并与BC的生长有关。NEDD4与临床病理参数相关,并预后不良。因此,NEDD4是预后不良的潜在生物标志物,也是BC治疗的潜在治疗靶标。BCLNM中的亚组分析显示,NEDD4高表达与复发风险升高相关(P = 0.0276)。此外,NEDD4表达是独立的预后指标。最后,NEDD4染色阳性的患者10年总生存率和无病生存率显着低于NEDD4染色阴性的BC患者(分别为P = 0.0024和P = 0.0011)。结论NEDD4表达在BC中升高,并与BC的生长有关。NEDD4与临床病理参数相关,并预后不良。因此,NEDD4是预后不良的潜在生物标志物,也是BC治疗的潜在治疗靶标。NEDD4染色阳性的患者10年总生存率和无病生存率显着低于BC NEDD4染色阴性的BC患者(分别为P = 0.0024和P = 0.0011)。结论NEDD4表达在BC中升高,并与BC的生长有关。NEDD4与临床病理参数相关,并预示不良预后。因此,NEDD4是预后不良的潜在生物标志物,也是BC治疗的潜在治疗靶标。NEDD4染色阳性的患者10年总生存率和无病生存率显着低于BC NEDD4染色阴性的BC患者(分别为P = 0.0024和P = 0.0011)。结论NEDD4表达在BC中升高,并与BC的生长有关。NEDD4与临床病理参数相关,并预后不良。因此,NEDD4是预后不良的潜在生物标志物,也是BC治疗的潜在治疗靶标。NEDD4与临床病理参数相关,并预后不良。因此,NEDD4是预后不良的潜在生物标志物,也是BC治疗的潜在治疗靶标。NEDD4与临床病理参数相关,并预后不良。因此,NEDD4是预后不良的潜在生物标志物,也是BC治疗的潜在治疗靶标。
更新日期:2020-04-22
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