Department of Otolaryngology-Head and Neck Surgery, Technical University of Munich, Ismaninger Straße 22, 81675 Muenchen, Germany.
Institute of Medical Informatics Statistics and Epidemiology, Technical University of Munich, Ismaninger Straße 22, 81675 Muenchen, Germany.
Int J Mol Sci. 2018 Mar 13;19(3):830. doi: 10.3390/ijms19030830.
The clinical impact of the expression of NOTCH1 signaling components in squamous cell carcinoma of the pharynx and larynx has only been evaluated in subgroups. The aim of this study was therefore to evaluate NOTCH1 expression in head and neck squamous cell cancer (HNSCC) patient tissue and cell lines. We analyzed tissue from 195 HNSCCs and tissue from 30 normal patients for mRNA expression of NOTCH1, NOTCH3, HES1, HEY1, and JAG1 using quantitative real-time PCR. Association of expression results and clinical orpathological factors was examined with multivariate Cox regression. NOTCH1 expression was determined in three Human Papilloma Virus (HPV)-positive and nine HPV-negative HNSCC cell lines. High expression of NOTCH1 was associated with better overall survival ( = 0.013) and disease-free survival ( = 0.040). Multivariate Cox regression confirmed the significant influence of NOTCH1 expression on overall survival ( = 0.033) and disease-free survival ( = 0.029). A significant correlation was found between p16 staining and NOTCH1 mRNA expression (correlation coefficient 0.28; = 0.01). NOTCH1 was expressed at higher levels in HPV-positive HNSCC cell lines compared with HPV-negative cell lines, which was not statistically significant ( = 0.068). We conclude that NOTCH1 expression is associated with overall survival, and that inhibition of NOTCH1 therefore seems less promising.
NOTCH1 信号通路成分在咽和喉鳞状细胞癌中的表达的临床影响仅在亚组中进行了评估。因此，本研究旨在评估头颈部鳞状细胞癌（HNSCC）患者组织和细胞系中 NOTCH1 的表达。我们使用定量实时 PCR 分析了 195 例 HNSCC 组织和 30 例正常患者组织中 NOTCH1、NOTCH3、HES1、HEY1 和 JAG1 的 mRNA 表达。使用多变量 Cox 回归分析表达结果与临床病理因素的相关性。在三种人乳头瘤病毒（HPV）阳性和九种 HPV 阴性 HNSCC 细胞系中测定 NOTCH1 的表达。NOTCH1 高表达与总生存（ = 0.013）和无病生存（ = 0.040）相关。多变量 Cox 回归证实 NOTCH1 表达对总生存（ = 0.033）和无病生存（ = 0.029）有显著影响。p16 染色与 NOTCH1 mRNA 表达之间存在显著相关性（相关系数 0.28； = 0.01）。与 HPV 阴性细胞系相比，HPV 阳性 HNSCC 细胞系中 NOTCH1 的表达水平更高，但无统计学意义（ = 0.068）。我们得出结论，NOTCH1 的表达与总生存率相关，因此抑制 NOTCH1 似乎不太有希望。
