A 26-gene hypoxia signature predicts benefit from hypoxia-modifying therapy in laryngeal cancer but not bladder cancer.
A 26-gene hypoxia signature predicts benefit from hypoxia-modifying therapy in laryngeal cancer but not bladder cancer.
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DOI：
10.1158/1078-0432.ccr-13-0542
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发表时间：
2013-09-01
期刊：
影响因子：
--
通讯作者：
West CM
中科院分区：
文献类型：
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作者：
Eustace A;Mani N;Span PN;Irlam JJ;Taylor J;Betts GN;Denley H;Miller CJ;Homer JJ;Rojas AM;Hoskin PJ;Buffa FM;Harris AL;Kaanders JH;West CM
在头颈癌和膀胱癌中，肿瘤缺氧与不良预后相关，缺氧修饰可改善预后，缺氧状态可预测治疗获益。然而，临床缺氧还没有通用的测量方法。这项研究的目的是调查是否有26个基因的缺氧标志预测在两种癌症类型的缺氧改善治疗的好处。样本来自157例T2-T4喉癌和185例T1-T4 a膀胱癌患者，这些患者分别参加了单独放疗或加用卡波津和烟酰胺（CON）的ARCON和BCON III期随机试验。定制的TaqMan低密度阵列（TLDAs）用于使用定量实时PCR评估26个基因标签的表达。26个基因的中值表达用于推导缺氧评分（HS）。患者被分类为TLDA-HS低（≤中位数）或TLDA-HS高（>中位数）。主要结局指标是区域控制（RC; ARCON）和总生存期（OS; BCON）。与TLDA-HS低的肿瘤相比，TLDA-HS高的喉肿瘤显示出更大的ARCON获益。TLDA-HS高水平组的五年RC为81%（单独放疗），而TLDA-HS高水平组的五年RC为100%（CON）（P=0.009）。对于TLDA-HS，低5年RC为91%（单独放疗）与90%（CON）（P=0.90）。TLDA-HS不能预测膀胱癌患者从CON中获益。26个基因的低氧标记预测喉癌患者从低氧修饰治疗中获益这些发现将在前瞻性临床试验中进行评价。
In head and neck and bladder cancer tumor hypoxia is associated with a poor prognosis, hypoxia modification improves outcome and hypoxic status predicts benefit from treatment. Yet, there is no universal measure of clinical hypoxia. The aim of this study was to investigate whether a 26-gene hypoxia signature predicted benefit from hypoxia-modifying treatment in both cancer types. Samples were available from 157 T2-T4 laryngeal cancer and 185 T1-T4a bladder cancer patients enrolled on the ARCON and BCON phase III randomized trials of radiotherapy alone or with carbogen and nicotinamide (CON) respectively. Customized TaqMan Low Density Arrays (TLDAs) were used to assess expression of the 26-gene signature using quantitative real-time PCR. The median expression of the 26 genes was used to derive a hypoxia score (HS). Patients were categorized as TLDA-HS low (≤median) or TLDA-HS high (>median). The primary outcome measures were regional control (RC; ARCON) and overall survival (OS; BCON). Laryngeal tumors categorized as TLDA-HS high showed greater benefit from ARCON than TLDA-HS low tumors. Five-year RC was 81% (radiotherapy alone) versus 100% (CON) for TLDA-HS high (P=0.009). For TLDA-HS low five-year RC was 91% (radiotherapy alone) versus 90% (CON) (P=0.90). TLDA-HS did not predict benefit from CON in bladder cancer. The 26-gene hypoxia signature predicts benefit from hypoxia-modifying treatment in laryngeal cancer. These findings will be evaluated in a prospective clinical trial.