Translational Radiobiology Group, Division of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Christie NHS Foundation Trust Hospital, Manchester, UK.
Translational Oncogenomics, Cancer Research UK Manchester Institute, Oglesby Cancer Research Building, University of Manchester, Manchester, UK.
Br J Cancer. 2021 Jul;125(1):85-93. doi: 10.1038/s41416-021-01326-9. Epub 2021 Apr 12.
miRNAs are promising biomarkers in oncology as their small size makes them less susceptible to degradation than mRNA in FFPE tissue. We aimed to derive a hypoxia-associated miRNA signature for bladder cancer.
Taqman miRNA array cards identified miRNA seed genes induced under hypoxia in bladder cancer cell lines. A signature was derived using feature selection methods in a TCGA BLCA training data set. miRNA expression data were generated for 190 tumours from the BCON Phase 3 trial and used for independent validation.
A 14-miRNA hypoxia signature was derived, which was prognostic for poorer overall survival in the TCGA BLCA cohort (n = 403, p = 0.001). Univariable analysis showed that the miRNA signature predicted an overall survival benefit from having carbogen-nicotinamide with radiotherapy (HR = 0.30, 95% CI 0.094-0.95, p = 0.030) and performed similarly to a 24-gene mRNA signature (HR = 0.47, 95% CI 0.24-0.92, p = 0.025). Combining the signatures improved performance (HR = 0.26, 95% CI 0.08-0.82, p = 0.014) with borderline significance for an interaction test (p = 0.065). The interaction test was significant for local relapse-free survival LRFS (p = 0.033).
A 14-miRNA hypoxia signature can be used with an mRNA hypoxia signature to identify bladder cancer patients benefitting most from having carbogen and nicotinamide with radiotherapy.
miRNAs 是肿瘤学中有前途的生物标志物，因为它们的小尺寸使它们在 FFPE 组织中比 mRNA 更不易降解。我们旨在为膀胱癌衍生出一个与缺氧相关的 miRNA 特征。
Taqman miRNA 阵列卡鉴定了在膀胱癌细胞系中缺氧诱导的 miRNA 种子基因。在 TCGA BLCA 训练数据集使用特征选择方法导出一个特征。为 BCON 阶段 3 试验的 190 个肿瘤生成了 miRNA 表达数据，并用于独立验证。
衍生出一个由 14 个 miRNA 组成的缺氧特征，在 TCGA BLCA 队列中（n=403，p=0.001）对总体生存率有预后意义。单变量分析表明，miRNA 特征预测了接受卡波金-烟酰胺联合放疗的总体生存获益（HR=0.30，95%CI 0.094-0.95，p=0.030），与 24 个基因 mRNA 特征的表现相似（HR=0.47，95%CI 0.24-0.92，p=0.025）。组合特征可改善（HR=0.26，95%CI 0.08-0.82，p=0.014）性能，交互检验（p=0.065）有边界显著意义。交互检验对局部无复发生存率（LRFS）有显著意义（p=0.033）。
一个 14 个 miRNA 缺氧特征可与一个 mRNA 缺氧特征一起用于鉴定最受益于卡波金和烟酰胺联合放疗的膀胱癌患者。
