PDF(Pubmed)
Abstract：
Glioblastoma multiforme (GBM) IDH-wildtype is the most prevalent brain malignancy in adults. However, molecular mechanisms, which leads to GBM have not been completely elucidated. Granulocyte colony-stimulating factor (GCSF), Granulocyte colony-stimulating factor receptor GCSFR, and Signal transducers and activators of transcription 3 (STAT3) have been involved in the occurrence and development of various cancers, but their role in GBM is little known. Herein, we have investigated the gene and protein expression of GCSF, GCSFR, and STAT3 in 21 tissue biopsy samples and also in tumor associated normal tissue (TANT) samples derived from glioblastoma patients, which revealed significantly differential expression of these genes. To validate our findings, we performed a comprehensive integrated analysis of transcriptomic and proteomic profiling of respective genes by retrieving GBM RNA-sequence data from Genome Atlas Databases. GO and KEGG analysis revealed enrichment in disease-related pathways, such as JAK/STAT pathway activation, which were associated with GBM progression. We further performed computational docking analysis of potential drug candidate Nisin against GCSF, and the results were validated in vitro through cytotoxic activity assay using a human glioblastoma cell line SF-767 in a dose-dependent manner. Our comprehensive analysis reveals that GCSF augments glioma progression, and its blockade with anticancer bacteriocin peptide Nisin can potentially inhibit the growth and metastasis of GBM.
摘要：
多形性胶质母细胞瘤(GBM)IDH-野生型是成人中最常见的脑恶性肿瘤。然而,分子机制，导致GBM的原因尚未完全阐明。粒细胞集落刺激因子(GCSF),粒细胞集落刺激因子受体GCSFR,信号转导和转录激活因子3(STAT3)参与了多种癌症的发生和发展,但它们在GBM中的作用鲜为人知。在这里，我们研究了GCSF的基因和蛋白质表达，GCSFR,和STAT3在21个组织活检样本，也在肿瘤相关的正常组织（TANT）样本来源于胶质母细胞瘤患者，这揭示了这些基因的显著差异表达。为了验证我们的发现,通过从基因组图谱数据库检索GBMRNA序列数据,我们对各自基因的转录组和蛋白质组谱分析进行了综合整合分析.GO和KEGG分析揭示了疾病相关途径的富集，如JAK/STAT通路激活，与GBM进展相关。我们进一步进行了潜在候选药物Nisin对GCSF的计算对接分析，并使用人胶质母细胞瘤细胞系SF-767以剂量依赖性方式通过细胞毒性活性测定在体外验证结果。我们的综合分析表明，GCSF增加神经胶质瘤的进展，用抗癌细菌素肽Nisin阻断可以潜在地抑制GBM的生长和转移。
