Cancer stem cell characteristics, ALDH1 expression in the invasive front of nasopharyngeal carcinoma

Cancer stem cell characteristics, ALDH1 expression in the invasive front of nasopharyngeal carcinoma
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DOI:
10.1007/s00428-013-1508-z
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发表时间:
2014-01-01
期刊:
影响因子:
3.5
通讯作者:
Yao, Kai-tai
Yao, Kai-tai
中科院分区:
医学3区
文献类型:
--
作者:
Luo, Wei-ren;Yao, Kai-tai

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侵袭性肿瘤前沿是各种人类恶性肿瘤的生物侵袭性和上皮-间质转化(EMT)的基础。然而,关于鼻咽癌侵袭性肿瘤前沿的分子生物学特征却鲜有报道。此外,癌症干细胞(CSC)在肿瘤侵袭性前沿的特征及其与EMT的相关性也仍然难以捉摸。本研究旨在探讨肿瘤干细胞标志物乙醛脱氢酶1(aldehyde dehydrogenase 1,ALDH 1)在鼻咽癌浸润前沿的表达及其临床意义。免疫组化主要检测ALDH 1在鼻咽癌浸润前沿的表达。ALDH 1表达和EMT相关标志物之间的关系也进行了研究。ALDH 1在浸润前沿的表达与淋巴浸润(p < 0.001)、T分类(p = 0.001)、M分类(p < 0.001)、临床分期(p < 0.001)和局部复发(p = 0.008)密切相关。ALDH 1在浸润前沿的过表达导致鼻咽癌生存率下降,特别是在早期(T1-T2或N 0-N1)患者中(分别为p < 0.001和p = 0.002),尽管它不是独立的预后因素(p = 0.196)。此外,在NPC的浸润前沿,ALDH 1表达与EMT相关生物标志物E-钙粘蛋白(p = 0.026)、波形蛋白(p < 0.001)、骨膜蛋白(p < 0.001)和Snail(p < 0.001)显著相关,但与β-连环蛋白(p = 0.143)无关。我们的研究结果首次表明,ALDH 1在浸润前沿的表达与EMT的特征和肿瘤的侵袭性密切相关,这可能为NPC患者提供一个有用的预后指标。
The invasive tumor front underlies the biological aggressiveness and epithelial-mesenchymal transition (EMT) in various human malignances. However, the molecular and biological characteristics of invasive tumor front in NPC have rarely been described. Additionally, the features of cancer stem cells (CSCs) in the invasive front of tumors and its correlation with EMT also remain elusive. Our study was to investigate the expression of CSCs marker aldehyde dehydrogenase 1 (ALDH1) in the invasive front of nasopharyngeal carcinoma (NPC) and its clinical significance. Immunohistochemistry was mainly used to detect ALDH1 expression in the invasive front of NPC. The relationship between ALDH1 expression and EMT-associated markers was also examined. ALDH1 expression in the invasive front correlated strongly with lymphatic invasion (p < 0.001), T classification (p = 0.001), M classification (p < 0.001), clinical stage (p < 0.001), and local recurrence (p = 0.008). ALDH1 overexpression in the invasive front contributed to worse survival of NPC, particularly in patients with early stage (T1-T2 or N0-N1) (p < 0.001 and p = 0.002, respectively), though it was not an independent prognostic factor (p = 0.196). Furthermore, in the invasive front of NPC, ALDH1 expression correlated significantly with EMT-related biomarkers E-cadherin (p = 0.026), Vimentin (p < 0.001), Periostin (p < 0.001), and Snail (p < 0.001), but not with beta-catenin (p = 0.143). Our findings demonstrate first that ALDH1 expression in the invasive front links closely with EMT characteristics and tumor aggressiveness, which might provide a useful prognostic marker for NPC patients.