Department of Neurosurgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
Med Oncol. 2013 Mar;30(1):325. doi: 10.1007/s12032-012-0325-6. Epub 2013 Feb 3.
Glioblastoma multiforme (GBM) is characterized by poor therapeutic response and poor overall survival. It is crucial that more effective therapies be developed for the treatment of GBM. Inhibitor of DNA binding protein-1 (ID1) has been shown to maintain the self-renewal capacity of neural stem cells and might be involved in the therapeutic resistance of GBM. In the present study, we explored survival data from the The Cancer Genome Atalas database that were based on ID1 expression for patients diagnosed with primary GBMs. Interestingly, patients with high ID1 expression had better survival than patients with low ID1 expression, and a strong correlation was found between radiotherapy efficacy, ID1 expression, and overall survival. We further investigated the relationship between ID1 expression and the radiosensitivity of glioblastoma using glioblastoma cell lines. The clonogenic formation assay showed that U87 ID1-shRNA cells were much less sensitive to radiation. Moreover, both the results of the γH2AX foci staining assay and the comet assay further revealed that ID1 negatively regulates DNA repair processes by downregulating the expression of genes such as DNA ligase IV (LIG4) and ataxia-telangiectasia-mutated. Additionally, ID1 induces G2/M arrest in U87 cells. Taken together, these results suggest that ID1 may be a new prognostic marker for GBM and have important implications for the therapeutic strategies used to treat GBM patients.
多形性胶质母细胞瘤（GBM）的治疗反应差，总体生存率低。因此，开发更有效的治疗方法治疗 GBM 至关重要。抑制 DNA 结合蛋白 1（ID1）已被证明能维持神经干细胞的自我更新能力，并且可能参与 GBM 的治疗抵抗。在本研究中，我们探讨了基于原发性 GBM 患者 ID1 表达的癌症基因组图谱数据库中的生存数据。有趣的是，ID1 高表达的患者比 ID1 低表达的患者生存更好，并且发现放疗疗效、ID1 表达和总生存率之间存在很强的相关性。我们进一步研究了 ID1 表达与胶质母细胞瘤放射敏感性的关系，使用胶质母细胞瘤细胞系进行研究。集落形成实验表明，U87 ID1-shRNA 细胞对辐射的敏感性降低。此外，γH2AX 焦点染色实验和彗星实验的结果进一步表明，ID1 通过下调 DNA 连接酶 IV（LIG4）和共济失调毛细血管扩张突变（ATM）等基因的表达来负调控 DNA 修复过程。此外，ID1 诱导 U87 细胞 G2/M 期阻滞。综上所述，这些结果表明 ID1 可能是 GBM 的一个新的预后标志物，对治疗 GBM 患者的治疗策略具有重要意义。
