HPV status, cancer stem cell marker expression, hypoxia gene signatures and tumour volume identify good prognosis subgroups in patients with HNSCC after primary radiochemotherapy: A multicentre retrospective study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG)
HPV status, cancer stem cell marker expression, hypoxia gene signatures and tumour volume identify good prognosis subgroups in patients with HNSCC after primary radiochemotherapy: A multicentre retrospective study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG)
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DOI：
10.1016/j.radonc.2016.11.008
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发表时间：
2016-12-01
影响因子：
5.7
通讯作者：
Baumann, Michael
中科院分区：
文献类型：
--
作者：
Linge, Annett;Lohaus, Fabian;Baumann, Michael
目的：探讨肿瘤体积、人乳头瘤病毒(HPV)状态、肿瘤干细胞(CSC)标志物表达和低氧基因信号作为放射抵抗机制的潜在标志物，对同期接受直接放射化疗(RCTx)的局部晚期头颈部鳞状细胞癌(HNSCC)患者的影响。材料和方法：对158例口腔、口咽或下咽局部晚期HNSCC患者在6个DKTK配对部位进行治疗，回顾分析肿瘤体积、HPV DNA、p16过表达、P53表达、CSC标志物表达和低氧相关基因信号对RCTx预后的影响。结果：单因素COX回归分析显示肿瘤体积、p16过度表达、SLC3A2和CD44蛋白表达对LRC有显著影响。肿瘤低氧分类仅对小肿瘤有显著影响。在多变量分析中，发现肿瘤体积、SLC3A2表达和15个基因缺氧信号与LRC独立相关(CD44蛋白n/a，因为在CD44阴性组中没有事件)。Logistic模型显示，与仅考虑肿瘤体积的模型相比，包含CD44蛋白表达和p16过表达的模型显著提高了预测2年后LRC的性能。结论：肿瘤体积、HPV状态、CSC标志物表达和缺氧基因特征是预测局部晚期HNSCC患者接受RCTx治疗的潜在预后生物标志物。该研究还支持在生物标记物研究中一般应包括单个肿瘤体积，并且生物标记物组合优于单个参数。(C)2016爱思唯尔爱尔兰有限公司。保留所有权利。
Objective: To investigate the impact of the tumour volume, HPV status, cancer stem cell (CSC) marker expression and hypoxia gene signatures, as potential markers of radiobiological mechanisms of radioresistance, in a contemporary cohort of patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who received primary radiochemotherapy (RCTx).Materials and Methods: For 158 patients with locally advanced HNSCC of the oral cavity, oropharynx or hypopharynx who were treated at six DKTK partner sites, the impact of tumour volume, HPV DNA, p16 overexpression, p53 expression, CSC marker expression and hypoxia-associated gene signatures on outcome of primary RCTx was retrospectively analyzed. The primary endpoint of this study was loco regional control (LRC).Results: Univariate Cox regression revealed a significant impact of tumour volume, p16 overexpression, and SLC3A2 and CD44 protein expression on LRC. The tumour hypoxia classification showed a significant impact only for small tumours. In multivariate analyses an independent correlation of tumour volume, SLC3A2 expression, and the 15-gene hypoxia signature with LRC was identified (CD44 protein n/a because of no event in the CD44-negative group). Logistic modelling showed that inclusion of CD44 protein expression and p16 overexpression significantly improved the performance to predict LRC at 2 years compared to the model with tumour volume alone.Conclusions: Tumour volume, HPV status, CSC marker expression and hypoxia gene signatures are potential prognostic biomarkers for patients with locally advanced HNSCC, who were treated by primary RCTx. The study also supports that the individual tumour volumes should generally be included in biomarker studies and that panels of biomarkers are superior to individual parameters. (C) 2016 Elsevier Ireland Ltd. All rights reserved.