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醛脱氢酶1A1阳性癌症干细胞在局部晚期、转移性头颈部鳞状细胞癌患者中的预后意义

Prognostic significance of ALDH1A1-positive cancer stem cells in patients with locally advanced, metastasized head and neck squamous cell carcinoma.

作者信息

Qian Xu, Wagner Steffen, Ma Chenming, Coordes Annekatrin, Gekeler Julia, Klussmann Jens P, Hummel Michael, Kaufmann Andreas M, Albers Andreas E

机构信息

Department of Otolaryngology, Head and Neck Surgery, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, 12200, Berlin, Germany.

出版信息

J Cancer Res Clin Oncol. 2014 Jul;140(7):1151-8. doi: 10.1007/s00432-014-1685-4. Epub 2014 Apr 27.

Abstract

PURPOSE

Aldehyde dehydrogenase 1 (ALDH1A1) has now been recognized as a cancer stem(-like) cells (CSCs) marker in various tumors including head and neck squamous cell carcinoma (HNSCC). The objective of this study was to examine the expression of ALDH1A1 in patients with locally advanced, metastasized HNSCC and to determine its prognostic value.

METHODS

Human papillomavirus genotypes and expression of ALDH1A1, Twist1, and p16 were analyzed in specimens of 81 patients with primary HNSCC and 49 lymph node metastases. Patient clinicopathologic and follow-up data were analyzed.

RESULTS

Expression of ALDH1A1 was observed in 38 (46.9 %) of 81 primary tumors and 26 (53 %) of 49 lymph node metastases, respectively. Notably, the expression of ALDH1A1 was correlated significantly with poor tumor differentiation grade (p = 0.011). Interestingly, ALDH1A1 was observed co-expressed with Twist1 in primary tumor and lymph node metastases. Multivariate analysis showed that ALDH1A1 expression predicted poor prognosis in patients with HNSCC (p = 0.011) and the subgroup of oropharyngeal squamous cell carcinoma (p = 0.001). In the patient cohort with advanced, metastasized tumors, ALDH1A1 was identified as independent predictor of overall survival in both groups.

CONCLUSIONS

Our results provide evidence for the prognostic value of ALDH1A1 as a CSC marker in patients with locally advanced, metastasized HNSCC.

摘要

目的

醛脱氢酶1(ALDH1A1)现已被公认为包括头颈部鳞状细胞癌(HNSCC)在内的多种肿瘤中的癌症干细胞(样)细胞(CSC)标志物。本研究的目的是检测局部晚期转移性HNSCC患者中ALDH1A1的表达,并确定其预后价值。

方法

分析了81例原发性HNSCC患者和49例淋巴结转移患者标本中的人乳头瘤病毒基因型以及ALDH1A1、Twist1和p16的表达。对患者的临床病理和随访数据进行了分析。

结果

在81例原发性肿瘤中,38例(46.9%)检测到ALDH1A1表达;在49例淋巴结转移中,26例(53%)检测到ALDH1A1表达。值得注意的是,ALDH1A1的表达与肿瘤低分化程度显著相关(p = 0.011)。有趣的是,在原发性肿瘤和淋巴结转移中均观察到ALDH1A1与Twist1共表达。多因素分析显示,ALDH1A1表达可预测HNSCC患者预后不良(p = 0.011)以及口咽鳞状细胞癌亚组患者预后不良(p = 0.001)。在晚期转移性肿瘤患者队列中,ALDH1A1被确定为两组总生存的独立预测因子。

结论

我们的结果为ALDH1A1作为局部晚期转移性HNSCC患者CSC标志物的预后价值提供了证据。

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