Biterge-Sut Burcu
Nigde Omer Halisdemir University, Faculty of Medicine, Department of Medical Biology, Nigde, Turkey.
Arq Neuropsiquiatr. 2020 Jan;78(1):34-38. doi: 10.1590/0004-282X20190131.
Brain tumors are one of the most common causes of cancer-related deaths around the world. Angiogenesis is critical in high-grade malignant gliomas, such as glioblastoma multiforme. The aim of this study is to comparatively analyze the angiogenesis-related genes, namely VEGFA, VEGFB, KDR, CXCL8, CXCR1 and CXCR2 in LGG vs. GBM to identify molecular distinctions using datasets available on The Cancer Genome Atlas (TCGA).
DNA sequencing and mRNA expression data for 514 brain lower grade glioma (LGG) and 592 glioblastoma multiforme (GBM) patients were acquired from The Cancer Genome Atlas (TCGA), and the genetic alterations and expression levels of the selected genes were analyzed.
We identified six distinct KDR mutations in the LGG patients and 18 distinct KDR mutations in the GBM patients, including missense and nonsense mutations, frame shift deletion and altered splice region. Furthermore, VEGFA and CXCL8 were significantly overexpressed within GBM patients.
VEGFA and CXCL8 are important factors for angiogenesis, which are suggested to have significant roles during tumorigenesis. Our results provide further evidence that VEGFA and CXCL8 could induce angiogenesis and promote LGG to progress into GBM. These findings could be useful in developing novel targeted therapeutics approaches in the future.
脑肿瘤是全球癌症相关死亡的最常见原因之一。血管生成在高级别恶性胶质瘤（如多形性胶质母细胞瘤）中至关重要。本研究的目的是比较分析低级别胶质瘤（LGG）与胶质母细胞瘤（GBM）中血管生成相关基因，即VEGFA、VEGFB、KDR、CXCL8、CXCR1和CXCR2，以利用癌症基因组图谱（TCGA）上的可用数据集识别分子差异。
从癌症基因组图谱（TCGA）获取514例低级别脑胶质瘤（LGG）和592例多形性胶质母细胞瘤（GBM）患者的DNA测序和mRNA表达数据，并分析所选基因的基因改变和表达水平。
我们在LGG患者中鉴定出6种不同的KDR突变，在GBM患者中鉴定出18种不同的KDR突变，包括错义突变和无义突变、移码缺失和剪接区域改变。此外，VEGFA和CXCL8在GBM患者中显著过表达。
VEGFA和CXCL8是血管生成的重要因素，提示它们在肿瘤发生过程中具有重要作用。我们的结果提供了进一步的证据，表明VEGFA和CXCL8可诱导血管生成并促进LGG进展为GBM。这些发现可能对未来开发新的靶向治疗方法有用。
