Assessment of cancer stem cell marker expression in primary head and neck squamous cell carcinoma shows prognostic value for aldehyde dehydrogenase (ALDH1A1)
Assessment of cancer stem cell marker expression in primary head and neck squamous cell carcinoma shows prognostic value for aldehyde dehydrogenase (ALDH1A1)
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DOI：
10.1016/j.ejphar.2019.172837
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发表时间：
2020-01-15
影响因子：
5
通讯作者：
Szczepanski, Miroslaw J.
中科院分区：
文献类型：
--
作者：
Szafarowski, Tomasz;Sierdzinski, Janusz;Szczepanski, Miroslaw J.
肿瘤干细胞（cancer stem cells，CSCs）在头颈部鳞状细胞癌（head and neck squamous cell carcinoma，HNSCC）的发生、发展过程中起着重要作用。最常见的指示CSC的标志物是：CD 44、CD 24、CD 133、ALDH 1A 1。我们的目的是评估CSC标志物在HNSCC.The研究包括49例原发性HNSCC，11例上呼吸道上皮异常增生和12例正常咽粘膜作为对照组治疗的患者的预后潜力。通过免疫组化评估四种CSC标志物的频率和表达水平。单因素和多因素分析CSC表达水平与肿瘤分期、淋巴结转移和总生存期的相关性，肿瘤组织中广泛表达CD 44、CD 24、CD 133、ALDH 1A 1，而癌组织中CD 44表达较高（P = 0.001）。发现ALDH 1A 1表达水平在T3-T4肿瘤中显著高于T1-T2肿瘤（P = 0.05）。淋巴结转移瘤中CD 24（P = 0.01）和CD 133（P < 0.05）的表达明显高于原发瘤。多因素分析显示，ALDH 1A 1阴性肿瘤患者的总生存期（OS）是ALDH 1A 1阳性（ALDH 1A 1+）肿瘤患者的5.25倍（P = 0.01）。在单变量和多变量分析中，仅ALDH 1A 1阳性对HNSCC患者的OS具有显著影响（HR = 2.47，P = 0.02）JNSCC中CSC标志物表达的基于免疫组织化学的评估对HNSCC患者具有显著的预测意义。肿瘤中CSC的频率，特别是ALDH 1A 1+细胞的频率与这些患者的5年OS相关。
Cancer stem cells (CSCs) play a key role in carcinogenesis and progression of head and neck squamous cell carcinomas (HNSCC). The most common markers indicating for CSCs are: CD44, CD24, CD133, ALDH1A1. Our objective was to evaluate the prognostic potential of CSC markers in HNSCC.The study included 49 patients treated for primary HNSCC, 11 patients with upper respiratory tract epithelial dysplasia and 12 subjects with the normal pharyngeal mucosa as a control group. The frequency and expression levels of the four CSC markers were assessed by immunohistochemistry. Univariate and multivariate analyses were used to correlate CSC expression levels with tumor stage, lymph node metastases or overall survival (OS).CD44, CD24, CD133, ALDH1A1 were widely expressed in tumors, whereas CD44 was found to be higher in cancer tissue (P = 0.001). ALDH1A1 expression levels were found to be significantly higher in T3-T4 tumors vs. T1-T2 tumors (P = 0.05). Lymph node metastases had significantly higher expression levels of CD24 (P = 0.01) and CD133 (P < 0.05) than primary tumors. Multifactorial analysis revealed that overall survival (OS) for patients with ALDH1A1 negative tumors was 5.25 times higher than for patients with ALDH1A1 positive (ALDH1A1 +) tumors (P = 0.01). On univariate and multivariate analysis, only ALDH1A1 positivity had a significant effect on OS of HNSCC patients (HR = 2.47 for P = 0.02).Immunohistochemistry-based assessments of CSC marker expression in HNSCC has significant predictive implications for patients with HNSCC. The frequency of CSCs in the tumor, specifically of ALDH1A1 + cells correlated with five-year OS in these patients.