Doublecortin-like kinase 1 expression associates with breast cancer with neuroendocrine differentiation.
Doublecortin-like kinase 1 expression associates with breast cancer with neuroendocrine differentiation.
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双皮质素样激酶 1 表达与乳腺癌神经内分泌分化相关
DOI：
10.18632/oncotarget.6386
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发表时间：
2016-01-12
期刊：
影响因子：
--
通讯作者：
Tse GM
中科院分区：
文献类型：
--
作者：
Liu YH;Tsang JY;Ni YB;Hlaing T;Chan SK;Chan KF;Ko CW;Mujtaba SS;Tse GM
双重皮质醇样激酶1(DCLK1)是一种微管相关蛋白，近年来被认为是胃肠道肿瘤干细胞分化和预后不良的指标。然而，目前还不清楚该蛋白是否在乳腺癌中也起到了类似的作用。在这里，我们用免疫组织化学方法分析了DCLK1在大量浸润性乳腺癌(IBC)中的表达。DCKL1与较低的组织学分级、无淋巴管侵犯、纤维化灶、坏死灶和较低的PN分期有关(p≤0.045)。此外，雌激素受体和神经内分泌标记物也独立存在显著相关性(p≤0.019)，提示雌激素受体与神经内分泌分化相关。在目前的队列中，IBC-NED的预后比没有NED的管腔癌更差(风险比=1.756，p=0.041)。有趣的是，在IBC-NED组中，DCLK1被发现是一个良好的预后因素(风险比=0.288，p=0.011)。这些发现与胃肠道癌症的研究结果相反，表明DCLK1在不同类型的癌症中发挥不同的功能。在临床实践中，NED不是常规的评估，因此IBC-NED没有得到很好的研究。它的不良结局和显著的异质性值得更多的关注。DCLK1的表达有助于这一特殊肿瘤亚型的预后和治疗。
Doublecortin-like kinase 1 (DCLK1), a microtubule associated kinase, has recently been proposed to be a putative marker for stemness and adverse prognosis in gastrointestinal cancers. However, it is not clear whether the protein also plays similar roles in breast cancer. Here, the expression of DCLK1 was analyzed in a large cohort of invasive breast cancers (IBC) by immunohistochemistry. DCKL1 was associated with favorable clinico-pathologic features, namely lower histologic grade, absence of lymphovascular invasion, fibrotic focus, necrosis and lower pN stage (p≤0.045). Additionally, independent significant correlations were found with estrogen receptor and neuroendocrine markers (p ≤0.019), implicating its relationship with IBC with neuroendocrine differentiation (IBC-NED). In the current cohort, IBC-NED showed worse outcome than luminal cancers without NED (hazard ratio=1.756, p=0.041). Interestingly, within the IBC-NED group, DCLK1 was found to be a good prognostic factor (hazard ratio =0.288, p=0.011). These findings were in contrast to those in gastrointestinal cancers, suggesting different functional roles of DCLK1 in different types of cancers. In clinical practice, NED is not routinely assessed; thus IBC-NED are not well studied. Its poor outcome and significant heterogeneity warrants more attention. DCLK1 expression could aid in the prognostication and management of this special cancer subtype.