Tumour hypoxia is a major contribut

肿瘤缺氧是导致抗癌治疗耐药性的主要因素。鉴于针对低氧的治疗试验的结果令人失望，可能需要一种更具个性化的方法。在这里，我们表征与肿瘤缺氧相关的多组学分子特征，并确定与抗癌药的耐药性和药敏反应相关的分子变化。基于公认的缺氧基因表达特征，我们将来自癌症基因组图谱（TCGA）的大约10,000个肿瘤样品分为不同癌症类型的低氧评分高和评分低的组，并证明它们的预后相关性。然后，我们确定了与缺氧状态相关的各种类型的分子特征，这些特征与耐药性相关，但在某些情况下，还与药物敏感性相关，与低氧赋予耐药性的传统观点相反。我们进一步表明，低氧状态可影响121个临床可操作基因中的110个（90.9％），并且可以通过实验验证低氧对培养细胞对几种药物反应的预测作用。我们的研究提供了对肿瘤缺氧的全面分子水平的理解，可能对临床癌症治疗有实际意义

肿瘤缺氧是抗癌疗法耐药的主要原因。鉴于缺氧靶向治疗试验的结果令人失望，可能需要一种更加个性化的方法。在这里，我们描述与肿瘤缺氧相关的多细胞分子特征，并识别与抗癌药物的耐药反应和耐药反应相关的分子变化。基于一个成熟的缺氧基因表达特征，我们将大约10，000个肿瘤样本分类为癌症基因组图谱（TCGA）中不同癌症类型的缺氧分数高和低分组，并展示其预后关联。然后，我们确定与缺氧状态相关的各种类型的分子特征，这些特征与耐药性相关，但在某些情况下，也与药物敏感性有关，这与缺氧具有耐药性的传统观点形成对比。我们进一步显示，121 人中的 110 人（90.9%）临床上可操作的基因可能受缺氧状态的影响，并在实验中验证缺氧对培养细胞中多种药物反应的预测影响。我们的研究提供了对肿瘤缺氧的全面分子水平理解，并可能对临床癌症治疗产生实际影响

Tumour hypoxia is a major contributor to resistance to anticancer therapies. Given that the results of hypoxia-targeted therapy trials have been disappointing, a more personalized approach may be needed. Here, we characterize multi-omic molecular features associated with tumour hypoxia and identify molecular alterations that correlate with both drug-resistant and drugsensitive responses to anticancer drugs. Based on a well-established hypoxia gene expression signature, we classify about 10,000 tumour samples into hypoxia score-high and score-low groups across different cancer types from The Cancer Genome Atlas (TCGA) and demonstrate their prognostic associations. Then, we identify various types of molecular features associated with hypoxia status that correlate with drug resistance but, in some cases, also with drug sensitivity, contrasting the conventional view that hypoxia confers drug resistance. We further show that 110 out of 121 (90.9%) clinically actionable genes can be affected by hypoxia status and experimentally validate the predicted effects of hypoxia on the response to several drugs in cultured cells. Our study provides a comprehensive molecular-level understanding of tumour hypoxia and may have practical implications for clinical cancer therapy<br>