Clinical significance of Notch receptors in triple negative breast cancer.

H. Shah, Mittal Mistry, Nupur Patel, H. Vora
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Abstract

BACKGROUND The Notch signaling pathway is an evolutionary conserved cell signaling pathway that plays an indispensable role in essential developmental processes. Aberrant activation of Notch pathway is known to initiate wide array of diseases and cancers. OBJECTIVE To evaluate the clinical significance of Notch receptors in Triple Negative Breast Cancer. METHODS We evaluated the association between Notch receptors and clinicopathological parameters including disease-free survival and overall survival of one hundred TNBC patients by immunohistochemistry. RESULTS Positive expression of nuclear Notch1 receptor (18%) was found be significantly correlated with positive lymph node (p = 0.009), high BR score (p = 0.02) and necrosis (p = 0.004) while cytoplasmic expression of Notch2 receptor (26%) was significantly correlated with metastasis (p = 0.05), worse DFS (p = 0.05) and poor OS (p = 0.02) in TNBC patients. Membrane (18%) and cytonuclear (3%) Notch3 expression were significantly associated with poorly differentiated tumors (p = 0.007), high BR score (p = 0.002) and necrosis (p = 0.03) respectively. However, cytoplasmic Notch3 and Notch4 expression were negatively correlated with poor prognostic factors. CONCLUSIONS Our data indicated that Notch receptors play a key role in promoting TNBC and mainly, Notch2 may contribute to poor prognosis of the disease. Hence, it is implicated that Notch2 may serve as a potential biomarker and therapeutic target for TNBC.
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Notch受体在三阴性乳腺癌中的临床意义。
Notch信号通路是一种进化保守的细胞信号通路,在重要的发育过程中起着不可或缺的作用。Notch通路的异常激活可引发多种疾病和癌症。目的探讨Notch受体在三阴性乳腺癌中的临床意义。方法采用免疫组化方法评价Notch受体与100例TNBC患者无病生存期和总生存期等临床病理参数的关系。结果核Notch1受体阳性表达(18%)与TNBC患者淋巴结阳性(p = 0.009)、高BR评分(p = 0.02)、坏死(p = 0.004)显著相关,细胞质Notch2受体阳性表达(26%)与TNBC患者转移(p = 0.05)、DFS加重(p = 0.05)、OS恶化(p = 0.02)显著相关。细胞膜(18%)和细胞核(3%)表达Notch3分别与低分化肿瘤(p = 0.007)、高BR评分(p = 0.002)和坏死(p = 0.03)显著相关。然而,细胞质Notch3和Notch4的表达与不良预后因素呈负相关。结论Notch受体在TNBC的发生中起关键作用,Notch2可能是导致TNBC预后不良的主要原因。因此,Notch2可能作为TNBC的潜在生物标志物和治疗靶点。
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来源期刊
Breast disease
Breast disease Medicine-Oncology
CiteScore
1.80
自引率
0.00%
发文量
59
期刊介绍: The recent expansion of work in the field of breast cancer inevitably will hasten discoveries that will have impact on patient outcome. The breadth of this research that spans basic science, clinical medicine, epidemiology, and public policy poses difficulties for investigators. Not only is it necessary to be facile in comprehending ideas from many disciplines, but also important to understand the public implications of these discoveries. Breast Disease publishes review issues devoted to an in-depth analysis of the scientific and public implications of recent research on a specific problem in breast cancer. Thus, the reviews will not only discuss recent discoveries but will also reflect on their impact in breast cancer research or clinical management.
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