Associations Between TFPI-2 Methylation and Poor Prognosis in Glioblastomas Paulina Vaitkienė, Daina Skiriutė, Kęstutis Skauminas

Paulina Vaitkienė,Arimantas Tamašauskas,Kęstutis Skauminas,Daina Skiriutė

doi:10.3390/medicina48070051

Paulina Vaitkienė, Arimantas Tamašauskas + Show 2 more

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https://doi.org/10.3390/medicina48070051

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Abstract

Background and Objective. The epigenetic silencing of tumor suppressor genes plays an important role in gliomagenesis. Recently, tissue factor pathway inhibitor 2 (TFPI-2) has been suggested as a tumor suppressor gene involved in tumorigenesis and metastasis in some cancers. However, to date, little is known about the methylation status of TFPI-2 gene in glioblastoma tissues. In this study, we aimed to investigate the methylation status of TFPI-2 promoter and its associations with patient prognosis in glioblastoma. Material and Methods. The methylation status of TFPI-2 was investigated by methylationspecific polymerase chain reaction in 99 glioblastoma patients. The associations between patients’ clinical variables and overall survival time were assessed. Results. TFPI-2 was aberrantly methylated in 22.2% (22/99) of glioblastoma tumors, but was not methylated in normal brain samples. The survival of patients with glioblastoma differed significantly between the methylated and unmethylated TFPI-2 groups (P=0.047). The 2-year survival among patients carrying methylated TFPI-2 tumors was significantly lower compared with that of patients with unmethylated TFPI-2 (27% versus 4.7%, P=0.037). Conclusions. The present work demonstrated that the epigenetic inactivation of TFPI-2 by promoter hypermethylation was a frequent and tumor-specific event in glioblastoma, and TFPI-2 promoter methylation might be considered as a prognostic marker in glioblastoma.

Highlights

Glioblastoma is one of the greatest challenges in the management of cancer patients worldwide, despite notable recent achievements in oncology
The present work demonstrated that the epigenetic inactivation of tissue factor pathway inhibitor 2 (TFPI-2) by promoter hypermethylation was a frequent and tumor-specific event in glioblastoma, and TFPI-2 promoter methylation might be considered as a prognostic marker in glioblastoma
The methylation status of the TFPI-2 promoter in glioblastoma tumor samples was detected by the methylation-specific polymerase chain reaction (MS-PCR) assay

Summary

Introduction

Glioblastoma is one of the greatest challenges in the management of cancer patients worldwide, despite notable recent achievements in oncology. Even with aggressive surgical resections, along with recent advances in radiotherapy and chemotherapy, the prognosis for glioblastoma patients remains dismal: the median survival after diagnosis is about 14 months. New markers are being investigated, which may help better diagnose and predict the course of glioblastoma. Glioblastoma is caused by an accumulation of genetic and epigenetic alterations. Gene silencing by the hypermethylation of CpG islands in the promoter regions is a common epigenetic abnormality in cancer and may lead to a loss of function of tumor suppressor gene. Identifying the aberrantly methylated genes may provide better understanding of the pathogenesis of glioblastoma and help for the development of novel tumor markers and therapeutic targets

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