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首页> 外文期刊>EBioMedicine >Development and Validation of a 28-gene Hypoxia-related Prognostic Signature for Localized Prostate Cancer
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Development and Validation of a 28-gene Hypoxia-related Prognostic Signature for Localized Prostate Cancer

机译：28基因缺氧相关的局部前列腺癌的预后签名的发展和验证。

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Background Hypoxia is associated with a poor prognosis in prostate cancer. This work aimed to derive and validate a hypoxia-related mRNA signature for localized prostate cancer. Method Hypoxia genes were identified in vitro via RNA-sequencing and combined with in vivo gene co-expression analysis to generate a signature. The signature was independently validated in eleven prostate cancer cohorts and a bladder cancer phase III randomized trial of radiotherapy alone or with carbogen and nicotinamide (CON). Results A 28-gene signature was derived. Patients with high signature scores had poorer biochemical recurrence free survivals in six of eight independent cohorts of prostatectomy-treated patients (Log rank test P ??.05), with borderline significances achieved in the other two ( P ??.1). The signature also predicted biochemical recurrence in patients receiving post-prostatectomy radiotherapy ( n ?=?130, P ?=?.007) or definitive radiotherapy alone ( n ?=?248, P ?=?.035). Lastly, the signature predicted metastasis events in a pooled cohort ( n ?=?631, P ?=?.002). Prognostic significance remained after adjusting for clinic-pathological factors and commercially available prognostic signatures. The signature predicted benefit from hypoxia-modifying therapy in bladder cancer patients (intervention-by-signature interaction test P ?=?.0026), where carbogen and nicotinamide was associated with improved survival only in hypoxic tumours. Conclusion A 28-gene hypoxia signature has strong and independent prognostic value for prostate cancer patients.
机译：背景低氧症与前列腺癌的不良预后有关。这项工作旨在得出和验证局部前列腺癌的低氧相关mRNA签名。方法通过RNA测序在体外鉴定低氧基因，并与体内基因共表达分析结合以产生特征。该签名在11个前列腺癌队列和单独或与碳源和烟酰胺（CON）放疗的膀胱癌III期随机试验中得到独立验证。结果获得了28个基因的签名。签名得分高的患者在接受前列腺切除术治疗的八个独立队列中有六个队列的生化无复发生存率较差（对数秩检验P 。05），在另两个队列中具有临界意义（P 。0.1）。 。该签名还预测了接受前列腺切除术后放疗（n = 130，P = 0.00007）或单独行明确放疗（n = 248，P = = 0.035）的患者的生化复发。最后，签名预测了合并队列中的转移事件（n = 631，P = 0.0002）。调整临床病理因素和市售预后标志后，预后意义仍然存在。签名预示着改良低氧疗法将有助于膀胱癌患者的获益（逐签名干预试验P = 0.0002），其中碳原和烟酰胺仅在低氧肿瘤中才具有改善的生存率。结论28基因缺氧信号对于前列腺癌患者具有较强的独立预后价值。

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