Metallothionein Genes are Highly Expressed in Malignant Astrocytomas and Associated with Patient Survival.

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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Masiulionytė B,Valiulytė I,Tamašauskas A,Skiriutė D

doi

10.1038/s41598-019-41974-9

subject

Has Abstract

pub_date

2019-04-01 00:00:00

pages

5406

issue

1

issn

2045-2322

pii

10.1038/s41598-019-41974-9

journal_volume

9

pub_type

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