缺氧诱导因子-1α 的表达预测浸润性膀胱癌缺氧修饰获益。
Expression of hypoxia-inducible factor-1α predicts benefit from hypoxia modification in invasive bladder cancer.
机构信息
Translational Radiobiology Group, Institute of Cancer Sciences, University of Manchester, Manchester Academic Health Centre, Christie Hospital, Wilmslow Road, Manchester M20 4BX, UK.
Department of Histopathology, Central Manchester University Hospitals NHS Foundation Trust, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK.
出版信息
Br J Cancer. 2014 Jul 29;111(3):437-43. doi: 10.1038/bjc.2014.315. Epub 2014 Jun 17.
BACKGROUND
The addition of carbogen and nicotinamide (CON) to radiotherapy (RT) improves overall survival in invasive bladder cancer. We explored whether expression of the hypoxia marker hypoxia-inducible factor-1α (HIF-1α) alone or in combination with other markers predicted benefit from CON.
METHODS
A retrospective study was carried out using material from patients with high-grade invasive bladder carcinoma enrolled in the BCON phase III trial of RT alone or with CON (RT+CON). HIF-1α expression was studied in 137 tumours using tissue microarrays and immunohistochemistry. Data were available from other studies for carbonic anhydrase IX and glucose transporter 1 protein and gene expression and tumour necrosis.
RESULTS
Patients with high HIF-1α expression had improved 5-year local relapse-free survival with RT+CON (47%) compared with RT alone (21%; hazard ratio (HR) 0.48, 95% CI 0.26-0.8, P=0.02), no benefit was seen with low HIF-1α expression (HR 0.81, 95% CI 0.43-1.50, P=0.5). Combinations of markers including necrosis also predicted benefit but did not improve on prediction using necrosis alone.
CONCLUSIONS
HIF-1α may be used to predict benefit from CON in patients with bladder cancer but does not improve on use of necrosis.
背景
在放射治疗（RT）中添加碳化氧和烟酰胺（CON）可提高浸润性膀胱癌的总生存率。我们探讨了缺氧标志物缺氧诱导因子-1α（HIF-1α）的单独表达或与其他标志物联合表达是否可预测接受 CON 治疗的获益。
方法
采用回顾性研究，对单独接受 RT 或接受 RT 联合 CON（RT+CON）治疗的高级别浸润性膀胱癌患者的材料进行了研究（BCON 三期试验）。使用组织微阵列和免疫组织化学方法对 137 个肿瘤中的 HIF-1α表达进行了研究。其他研究提供了碳酸酐酶 IX 和葡萄糖转运蛋白 1 蛋白和基因表达以及肿瘤坏死的数据。
结果
高 HIF-1α表达的患者在接受 RT+CON 治疗时（47%），5 年局部无复发生存率优于单独接受 RT（21%；危险比（HR）0.48，95%CI 0.26-0.8，P=0.02），低 HIF-1α表达的患者未见获益（HR 0.81，95%CI 0.43-1.50，P=0.5）。包括坏死在内的标志物组合也预测了获益，但与单独使用坏死相比并没有改善预测。
结论
HIF-1α可用于预测膀胱癌患者接受 CON 治疗的获益，但不能改善坏死的使用。
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