Abstract
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.
Highlights
Www.nature.com/scientificreports changes in tumour is not understood yet
Analysis of MT expression in patient age groups have shown that higher MT1A, MT2 and MT3 genes expression level was significantly associated with older patient age (>50 years) (Chisquare test, p < 0.05)
We performed a thorough analysis of metallothionein gene activity in I to IV grade astrocytomas
Summary
Www.nature.com/scientificreports changes in tumour is not understood yet. The expression level may depend on the differentiation of tumour, proliferation or gene mutations, for example, p5312. MT gene expression was associated with tumour grade and cell proliferation rate in germ cell carcinoma and breast cancer[12,15]. There is not enough information about MT gene expression changes in different grade gliomas. It is known that MT gene expression in glioblastoma tumour samples was related to shorter patients survival[16]. It is important to clarify the importance of MTs expression level change during malignant progression. The purpose of this study was to determine MT genes mRNA expression level in different grade glioma tumours and to disclose gene expression associated promoter methylation in gliomas
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