Laboratory of Molecular Neurooncology, Neuroscience Institute, Medical Academy, Lithuanian University of Health Sciences, Eiveniu str. 4, Kaunas, LT-50161, Lithuania.
Sci Rep. 2019 Apr 1;9(1):5406. doi: 10.1038/s41598-019-41974-9.
Gliomas are heterogeneous, primary brain tumours that originate from glial cells. The main type of gliomas is astrocytomas. There are four grades (I-IV) of astrocytoma malignancy. Astrocytoma grade IV known as glioblastoma multiforme (GBM) is the most common and aggressive type of astrocytic gliomas. Metallothioneins (MT) are low molecular weight, cysteine rich proteins encoded by a family of metallothionein (MT) genes. MT genes play a crucial role in carcinogenesis of diverse malignancies. We proposed MT genes as prognostic markers for malignant astrocytoma. MT1A, MT1E, MT1X, MT2, MT3 gene expression was elevated in grade IV astrocytomas (glioblastomas) as compared to astrocytomas grade I-III. Statistically significant differences were reached for MT1A and MT2 genes (Mann-Whitney test, p < 0.05). High MT1A, MT1X, MT2, MT3 genes expression was associated with shorter patient survival (Log-rank test, p < 0.05). MT1A gene promoter methylation was decreased in glioblastoma (57.6%) while the gene was highly methylated in grade II-III astrocytoma (from 66.7% to 83.3%) and associated with better patient survival (p < 0.05). MT1A gene methylation showed a trend of being associated with higher mRNA expression level in astrocytomas. Increased MT genes expression in grade IV astrocytomas as compared to I-III grade astrocytomas could be associated with malignant tumour behaviour and progression.
神经胶质瘤是起源于神经胶质细胞的异质性原发性脑肿瘤。神经胶质瘤的主要类型是星形细胞瘤。星形细胞瘤有四级（I-IV）恶性程度。星形细胞瘤 IV 级称为多形性胶质母细胞瘤（GBM），是最常见和侵袭性最强的星形细胞神经胶质瘤。金属硫蛋白（MT）是由金属硫蛋白（MT）基因家族编码的低分子量、富含半胱氨酸的蛋白质。MT 基因在多种恶性肿瘤的发生中起着至关重要的作用。我们提出 MT 基因作为恶性星形细胞瘤的预后标志物。与 I-III 级星形细胞瘤相比，IV 级星形细胞瘤（胶质母细胞瘤）中 MT1A、MT1E、MT1X、MT2、MT3 基因表达升高。MT1A 和 MT2 基因达到统计学显著差异（Mann-Whitney 检验，p<0.05）。MT1A、MT1X、MT2、MT3 基因高表达与患者生存时间缩短相关（Log-rank 检验，p<0.05）。胶质母细胞瘤中 MT1A 基因启动子甲基化降低（57.6%），而 II-III 级星形细胞瘤中基因高度甲基化（从 66.7%到 83.3%），并与患者生存时间延长相关（p<0.05）。MT1A 基因甲基化与星形细胞瘤中 mRNA 表达水平升高呈相关趋势。与 I-III 级星形细胞瘤相比，IV 级星形细胞瘤中 MT 基因表达增加可能与恶性肿瘤行为和进展有关。
