Boidot Romain, Branders Samuel, Helleputte Thibault, Rubio Laila Illan, Dupont Pierre, Feron Olivier
Institut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology and Therapeutics (FATH), Université catholique de Louvain, Brussels, Belgium. These authors contribued equally to this work.
Machine Learning Group, Institute of Information and Communication Technologies, Electronics and Applied Mathematics (ICTEAM), Université catholique de Louvain, Louvain-la-Neuve, Belgium. These authors contribued equally to this work.
Oncotarget. 2014 Aug 30;5(16):6947-63. doi: 10.18632/oncotarget.2285.
Temporal and local fluctuations in O2 in tumors require adaptive mechanisms to support cancer cell survival and proliferation. The transcriptome associated with cycling hypoxia (CycHyp) could thus represent a prognostic biomarker of cancer progression.
We exposed 20 tumor cell lines to repeated periods of hypoxia/reoxygenation to determine a transcriptomic CycHyp signature and used clinical data sets from 2,150 breast cancer patients to estimate a prognostic Cox proportional hazard model to assess its prognostic performance.
The CycHyp prognostic potential was validated in patients independently of the receptor status of the tumors. The discriminating capacity of the CycHyp signature was further increased in the ER+ HER2- patient populations including those with a node negative status under treatment (HR=3.16) or not (HR=5.54). The CycHyp prognostic signature outperformed a signature derived from continuous hypoxia and major prognostic metagenes (P<0.001). The CycHyp signature could also identify ER+HER2 node-negative breast cancer patients at high risk based on clinicopathologic criteria but who could have been spared from chemotherapy and inversely those patients classified at low risk based but who presented a negative outcome.
The CycHyp signature is prognostic of breast cancer and offers a unique decision making tool to complement anatomopathologic evaluation.
肿瘤中氧气的时间和局部波动需要适应性机制来支持癌细胞的存活和增殖。因此，与循环性缺氧（CycHyp）相关的转录组可能代表癌症进展的预后生物标志物。
我们将20种肿瘤细胞系暴露于反复的缺氧/复氧周期中，以确定转录组CycHyp特征，并使用来自2150例乳腺癌患者的临床数据集来估计预后Cox比例风险模型，以评估其预后性能。
CycHyp的预后潜力在患者中得到验证，与肿瘤的受体状态无关。在ER + HER2-患者群体中，包括那些接受治疗（HR = 3.16）或未接受治疗（HR = 5.54）的淋巴结阴性状态患者，CycHyp特征的鉴别能力进一步提高。CycHyp预后特征优于源自持续性缺氧和主要预后元基因的特征（P <0.001）。CycHyp特征还可以根据临床病理标准识别出高风险的ER + HER2淋巴结阴性乳腺癌患者，但这些患者本可以免于化疗，反之，那些根据低风险分类但出现阴性结果的患者。
CycHyp特征可预测乳腺癌预后，并提供一种独特的决策工具以补充解剖病理学评估。
