Robertson Emily, Perry Christina, Doherty Rachel, Madhusudan Srinivasan
Academic Unit of Oncology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham University Hospitals, Nottingham, U.K.
Academic Unit of Oncology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham University Hospitals, Nottingham, U.K. Department of Oncology, Nottingham University Hospitals, Nottingham, U.K.
Cancer Genomics Proteomics. 2015 May-Jun;12(3):103-12.
The Forkhead box transcription factor (FOX) family plays an essential role in embryogenesis, especially during brain development. Our hypothesis is that de-regulation of FOX genes may contribute to aggressive tumor biology and therapy resistance in patients with glioblastoma multiforme (GBM).
Univariate and multivariate analyses were performed to evaluate prognostic significance of transcript levels of 31 FOX genes in a test set of GBM patients (n=191) and validated them in The Cancer Genome Atlas (TCGA) cohort comprising of 508 adult cases of GBM. The predictive significance of key FOX genes was investigated in patients who received chemotherapy or radiotherapy.
Low FOXA2 mRNA, low FOXN2 mRNA, low FOXN3 mRNA and high FOXG1 mRNA were associated with poor survival in the test and TCGA validation cohorts. In multivariate analysis, low FOXA2 mRNA, low FOXN2 mRNA, low FOXN3 mRNA and high FOXG1 mRNA remained independently associated with poor survival in the test and TCGA validation cohorts. In patients who received chemotherapy or radiotherapy, low FOXA2 mRNA, low FOXN2 mRNA and high FOXG1 mRNA correlated with adverse outcomes in the TCGA validation cohort.
To our knowledge, our data provide the first comprehensive clinical evidence that FOXA2, FOXN2, FOXN3 and FOXG1 are promising biomarkers of GBM and warrant further investigation.
叉头框转录因子（FOX）家族在胚胎发育过程中，尤其是在脑发育过程中发挥着至关重要的作用。我们的假设是，FOX基因的失调可能导致多形性胶质母细胞瘤（GBM）患者出现侵袭性肿瘤生物学行为和治疗抵抗。
进行单变量和多变量分析，以评估31个FOX基因转录水平在一组GBM患者（n = 191）中的预后意义，并在由508例成年GBM病例组成的癌症基因组图谱（TCGA）队列中进行验证。对接受化疗或放疗的患者研究关键FOX基因的预测意义。
在测试队列和TCGA验证队列中，低FOXA2 mRNA、低FOXN2 mRNA、低FOXN3 mRNA和高FOXG1 mRNA与较差的生存率相关。在多变量分析中，低FOXA2 mRNA、低FOXN2 mRNA、低FOXN3 mRNA和高FOXG1 mRNA在测试队列和TCGA验证队列中仍与较差的生存率独立相关。在接受化疗或放疗的患者中，低FOXA2 mRNA、低FOXN2 mRNA和高FOXG1 mRNA与TCGA验证队列中的不良结局相关。
据我们所知，我们的数据提供了首个全面的临床证据，表明FOXA2、FOXN2、FOXN3和FOXG1是GBM有前景的生物标志物，值得进一步研究。
