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首页> 外文期刊>Oral oncology >YAP1 is a potential biomarker for cetuximab resistance in head and neck cancer
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YAP1 is a potential biomarker for cetuximab resistance in head and neck cancer

机译：YAP1是头颈部癌西妥昔单抗耐药的潜在生物标志物

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Objectives Targeted therapy against the epidermal growth factor receptor (EGFR) only variably represents a therapeutic advance in head and neck squamous cell carcinoma (HNSCC). This study addresses the need of biomarkers of treatment response to the EGFR-targeting antibody cetuximab (Erbitux?). Materials and Methods The intrinsic cetuximab sensitivity of HNSCC cell lines was assessed by a crystal violet assay. Gene copy number analysis of five resistant and five sensitive cell lines was performed using the Affymetrix SNP 6.0 platform. Quantitative real-time PCR was used for verification of selected copy number alterations and assessment of mRNA expression. The functional importance of the findings on the gene and mRNA level was investigated employing siRNA technology. The data was statistically evaluated using Mann-Whitney U-test and Spearman's correlation test. Results Analysis of the intrinsic cetuximab sensitivity of 32 HNSCC cell lines characterized five and nine lines as cetuximab sensitive or resistant, respectively. Gene copy number analysis of five resistant versus five sensitive cell lines identified 39 amplified protein-coding genes, including YAP1, in the genomic regions 11q22.1 or 5p13-15. Assessment using qPCR verified that YAP1 amplification associated with cetuximab resistance. Amplification of YAP1 correlated to higher mRNA levels, and RNA knockdown resulted in increased cetuximab sensitivity. Assessment of several independent clinical data sets in the public domain confirmed YAP1 amplifications in multiple tumor types including HNSCC, along with highly differential expression in a subset of HNSCC patients. Conclusion Taken together, we provide evidence that YAP1 could represent a novel biomarker gene of cetuximab resistance in HNSCC cell lines.
机译：目的针对表皮生长因子受体（EGFR）的靶向疗法仅可变地代表了头颈部鳞状细胞癌（HNSCC）的治疗进展。这项研究满足了对针对EGFR的抗体西妥昔单抗（Erbitux？）治疗反应的生物标志物的需求。材料和方法HNSCC细胞系的固有西妥昔单抗敏感性通过结晶紫测定法评估。使用Affymetrix SNP 6.0平台对五个耐药和五个敏感细胞系进行了基因拷贝数分析。实时定量PCR用于验证选择的拷贝数变化和mRNA表达的评估。利用siRNA技术研究了发现的基因和mRNA水平的功能重要性。使用Mann-Whitney U检验和Spearman的相关检验对数据进行统计学评估。结果分析了32个HNSCC细胞系固有的西妥昔单抗敏感性，其中5个和9个系分别为西妥昔单抗敏感或耐药。对五个抗性细胞对五个敏感细胞系的基因拷贝数分析确定了基因组区域11q22.1或5p13-15中的39个扩增的蛋白质编码基因，包括YAP1。使用qPCR进行的评估证实YAP1扩增与西妥昔单抗耐药相关。 YAP1的扩增与更高的mRNA水平相关，RNA敲低导致西妥昔单抗敏感性增加。对公共领域中几个独立临床数据集的评估证实了YAP1在包括HNSCC在内的多种肿瘤类型中的扩增，以及在一部分HNSCC患者中的高度差异表达。结论综上所述，我们提供的证据表明YAP1可以代表HNSCC细胞系中西妥昔单抗耐药性的新生物标记基因。

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