对患者肿瘤中个体低氧水平的生物学机制了解尚不充分。在本研究中，我们运用放射基因组学的方法，通过基于基因表达数据派生的生物学过程，鉴定了磁共振成像（MRI）基于低氧水平与前列腺癌相关的关联。我们为85例前列腺癌患者构建了基于MRI的低氧图像，这些图像是通过结合反映氧气消耗和供应的扩散加权图像来生成的。为了验证这些图像中低氧水平的可区分性，我们将其与与其相匹配的通过做苦甘酰胺染色的活检组织切片进行了比较。对于基于MRI定义的低氧水平，我们计算了相应的低氧分数，并将其与活检基因表达谱进行了相关性分析。基因集富集分析(GSEA)预测了生物学过程，并通过免疫组化(增殖标记物Ki67、反应性基质分级)和RT-PCR(MYC)进行了验证。我们鉴定了与56种基于MRI的低氧水平的表达水平和低氧分数之间存在相关性的基因。在所有水平上，GSEA鉴定了增殖作为相关基因中富集的主要生物学过程。我们发展了两个独立的增殖基因签名。Peak1签名在中度/重度低氧水平上上调，反映了pimonidazole阳性区域癌细胞中MYC上调和高Ki67增殖指数。Peak2签名在轻度至非低氧水平上调，与成纤维细胞基因签名和反应性基质分级相关。高得分的Peak1和Peak2都表示多个队列中生化复发风险升高。放射基因组学鉴定了在不同低氧水平下激活的两个基因表达程序，反映了癌细胞和基质细胞的增殖。参与这些程序的基因可能成为干预的潜在靶点。 © 2023 Elsevier B.V. 版权所有。

The biology behind individual hypoxia levels in patient tumors is poorly understood. Here, we used radiogenomics to identify associations between magnetic resonance imaging (MRI)-based hypoxia levels and biological processes derived from gene expression data in prostate cancer.For 85 prostate cancer patients, MRI-based hypoxia images were constructed by combining diffusion-weighted images reflecting oxygen consumption and supply. The ability to differentiate hypoxia levels in these images was verified by comparison with matched biopsy sections stained for the hypoxia marker pimonidazole. For MRI-defined hypoxia levels, corresponding hypoxic fractions were calculated and correlated with biopsy gene expression profiles. Biological processes were predicted by gene set enrichment analysis (GSEA) and validated by immunohistochemistry (Ki67 proliferation marker, reactive stroma grade) and RT-PCR (MYC).Genes with correlation between expression level and hypoxic fraction were identified for 56 MRI-based hypoxia levels. At all levels, GSEA identified proliferation as the predominant biological process enriched among the correlating genes. Two independent proliferative gene signatures were developed. The Peak1 signature, upregulated at moderate/severe hypoxia, reflected MYC upregulation and high Ki67-proliferation index of cancer cells in pimonidazole-positive regions. The Peak2 signature, upregulated at mild to non-hypoxic levels, was associated with fibroblast gene signature and reactive stroma grade. High scores of both Peak1 and Peak2 indicated elevated risk of biochemical recurrence in multiple cohorts.Radiogenomics identified two gene expression programs activated at different hypoxia levels, reflecting proliferation of cancer cells and stroma cells. Genes involved in these programs could be candidate targets for intervention.Copyright © 2023 Elsevier B.V. All rights reserved.