Distinctive role of SIRT1 expression on tumor invasion and metastasis in breast cancer by molecular subtype
Distinctive role of SIRT1 expression on tumor invasion and metastasis in breast cancer by molecular subtype
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DOI：
10.1016/j.humpath.2015.03.015
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发表时间：
2015-07-01
期刊：
影响因子：
3.3
通讯作者：
Ryu, Han Suk
中科院分区：
文献类型：
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作者：
Chung, Yul Ri;Kim, Hyojin;Ryu, Han Suk
本研究的目的是评估沉默交配型信息调节2同源物1（SIRT 1）的表达水平亚型，并评估其预测能力腋窝淋巴结转移（LNM）及其与临床结果的关联。共选择427例确诊为浸润性导管癌的患者，在组织芯片上进行SIRT 1表达的免疫组化染色，并与人乳腺癌细胞系的每个内在亚型进行体外实验。SIRT 1在激素受体阳性乳腺癌和HER 2乳腺癌亚型中表达增加与LNM风险降低显著相关。相反，在三阴性乳腺癌中，LNM阳性亚组比LNM阴性亚组更频繁地观察到SIRT 1表达增加。包括SIRT 1在内的具有统计学显著性的独立参数的组合揭示了LNM的预测性能，其中激素受体阳性乳腺癌、HER 2乳腺癌和三阴性乳腺癌亚型的曲线下面积分别为0.602、0.587和0.726。在MDA-MB-231中，用小干扰RNA抑制SIRT 1表达可特异性抑制肿瘤侵袭。这是第一个研究SIRT 1在乳腺癌中的表达亚型，我们已经观察到SIRT 1基因的潜在不同作用，具有肿瘤抑制或肿瘤促进的影响，这取决于亚型;因此，SIRT 1表达和预后亚型之间的不同关联应考虑在其靶向治疗。(C)2015 Elsevier Inc. All rights reserved.
The aim of this study was to evaluate silent mating type information regulation 2 homolog 1 (SIRT 1) expression levels by subtype and evaluate its predictive power of axillary lymph node metastasis (LNM) and its association with clinical outcome. A total of 427 patients diagnosed with invasive ductal carcinoma were chosen, immunohistochemical staining for SIRT1 expression was performed on tissue microarrays, and in vitro experiments with each intrinsic subtype of human breast cancer cell line were carried out. Increased expression of SIRT1 in hormone receptor positive breast cancer and HER2 breast cancer subtype significantly correlated with lower risks of LNM. On the contrary, in triple-negative breast cancer, increased SIRT1 expression was more frequently observed in LNM-positive subgroup than LNM-negative subgroup. Combination of statistically significant, independent parameters including SIRT1 revealed predictive performance for LNM with area under the curve of 0.602, 0.587, and 0.726 for hormone receptor positive breast cancer, HER2 breast cancer, and triple-negative breast cancer subtype, respectively. Inhibition of SIRT1 expression with small interfering RNA suppressed tumor invasion in MDA-MB-231, specifically. This is the first study to examine SIRT1 expression in breast cancer by subtype, and we have observed the potentially different role of SIRT1 gene having tumor-suppressive or tumor-promoting influence depending on the subtype; thus, different associations between SIRT1 expression and prognosis by subtype should be considered in its target therapy. (C) 2015 Elsevier Inc. All rights reserved.