Immunohistochemical determination of the miR-1290 target arylamine N-acetyltransferase 1 (NAT1) as a prognostic biomarker in breast cancer.
Immunohistochemical determination of the miR-1290 target arylamine N-acetyltransferase 1 (NAT1) as a prognostic biomarker in breast cancer.
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DOI：
10.1186/1471-2407-14-990
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发表时间：
2014-12-20
期刊：
影响因子：
3.8
通讯作者：
Toyama T
中科院分区：
文献类型：
--
作者：
Endo Y;Yamashita H;Takahashi S;Sato S;Yoshimoto N;Asano T;Hato Y;Dong Y;Fujii Y;Toyama T
雌激素受体α (ERα)阳性和ERα阴性乳腺癌存在许多分子差异。最近的分析表明，前者可分为腔内A和腔内b两种亚型，它们对内分泌治疗和化疗的反应以及预后不同。在之前的研究中，我们发现microRNA (miR)-1290在管腔a肿瘤及其潜在靶点芳胺n-乙酰转移酶1 （NAT1）中显著下调。本研究的目的是确定NAT1是否是miR-1290的真正靶点，并探讨NAT1对乳腺癌预后的影响。采用荧光素酶报告基因检测来验证NAT1作为推测的miR-1290靶基因。采用免疫组化方法分析394例乳腺癌标本中NAT1、ERα、孕激素受体（PgR）和HER2的表达。NAT1被证实是miR-1290的直接靶点。NAT1表达水平与ERα、PgR表达水平呈正相关（P < 0.0001），与肿瘤分级、肿瘤大小呈负相关（P < 0.0001）。Kaplan-Meier分析显示，NAT1的存在与这些患者总生存期（OS）的增加显著相关（P = 0.0416）。同样，在接受他莫昔芬辅助内分泌治疗的患者（n = 176）中，NAT1与无病生存（DFS） （P = 0.0048）和OS （P = 0.0055）存在显著相关性。此外，在淋巴结阳性患者亚组（n = 147）中，NAT1也与DFS （P = 0.0025）和OS （P = 0.0007）的增加显著相关。单因素和多因素分析显示，NAT1水平与DFS之间存在显著相关性（P分别为0.0005和0.019）。我们报道miR-1290直接靶向NAT1 3 ' -UTR， NAT1蛋白表达与乳腺癌患者OS改善相关。NAT1可能是淋巴结阳性乳腺癌的预后生物标志物。因此，miR-1290及其靶点NAT1与乳腺癌的重要特征相关。本文的在线版本（doi:10.1186/1471-2407-14-990）包含补充材料，可供授权用户使用。
There are many molecular differences between estrogen receptor α (ERα)-positive and ER-negative breast cancers. Recent analyses have shown that the former can be divided into two subtypes, luminal A and luminal B. These differ in response to endocrine therapy and chemotherapy, and in prognosis. In a previous study, we found that microRNA (miR)-1290 that was significantly down-regulated in luminal A tumors and its potential target arylamine N-acetyltransferase 1 (NAT1). The aim of the present study was to determine whether NAT1 is a bona fide target of miR-1290, and to investigate the impact of NAT1 on breast cancer prognosis. Luciferase reporter assays were employed to validate NAT1 as a putative miR-1290 target gene. Expression of NAT1, ERα, progesterone receptor (PgR) and HER2 was analyzed in 394 breast cancer samples by immunohistochemistry. NAT1 was confirmed to be a direct target of miR-1290. Levels of expression of NAT1 were positively correlated with those of ERα (P < 0.0001) and PgR (P < 0.0001), but negatively correlated with both tumor grade and size (P < 0.0001). Kaplan-Meier analysis showed that the presence of NAT1 was significantly associated with increased overall survival (OS) (P = 0.0416) in these patients. Similarly, significant associations of NAT1 with disease-free survival (DFS) (P = 0.0048) and OS (P = 0.0055) in those patients who received adjuvant endocrine therapy with tamoxifen (n = 176) were found. Moreover, NAT1 was also significantly associated with increased DFS (P = 0.0025) and OS (P = 0.0007) in the subset of lymph node-positive patients (n = 147). Univariate and multivariate analyses showed significant associations between levels of NAT1 and DFS (P = 0.0005 and 0.019, respectively). We report that miR-1290 directly targets the NAT1 3′-UTR and that NAT1 protein expression is correlated with improved OS of breast cancer patients. NAT1 is a possible prognostic biomarker for lymph node-positive breast cancer. Thus, miR-1290 and its target NAT1 are associated with important characteristics of breast cancer. The online version of this article (doi:10.1186/1471-2407-14-990) contains supplementary material, which is available to authorized users.
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DOI：
10.1016/j.bbrc.2010.01.087
发表时间：
2010-02-26
影响因子：
3.1
作者：
Tiang, Jacky M.;Butcher, Neville J.;Minchin, Rodney F.
通讯作者：
Minchin, Rodney F.
影响因子：
4.8
作者：
Adam, PJ;Boyd, R;Terrett, JA
通讯作者：
Terrett, JA
影响因子：
3.7
作者：
Tiang, Jacky M.;Butcher, Neville J.;Minchin, Rodney F.
通讯作者：
Minchin, Rodney F.
芳基胺N-乙酰转移酶：从药物代谢和药物遗传学到药物发现。
影响因子：
7.3
作者：
Sim E;Abuhammad A;Ryan A
通讯作者：
Ryan A
DOI：
10.1073/pnas.0932692100
发表时间：
2003-07-08
影响因子：
11.1
作者：
Sorlie, T;Tibshirani, R;Botstein, D
通讯作者：
Botstein, D