臨床研究ジャーナル

Homocysteine, Genomic DNA Methylation and Cell-free DNA Levels as Biomarkers for Glioblastoma Patient's Outcome

Abstract

Thereza Quirico-Santos

Introduction: Glioblastoma (GBM) is characterized by recurrence (rGBM), resistance to chemotherapy and low life expectancy. The methyl grouping pathway plays a crucial role in macromolecule synthesis, gene expression control and maintenance of cellular redox balance. Under physiological conditions, the clearance pathways of homocysteine (Hcys) do not exist in the brain. This work aimed to determine circulating homocysteine levels according to the location of the tumor lesion (lobar or deep).

Material and methods: Hcys was dosed by enzymatic method in the serum of 61 patients at the time of inclusion in the Phase I/II study protocol (CONEP 9681 no: 25000.009627/2004-25). Medians were compared between the groups according to tumor location and statistical significance by effect size. Moreover, statistical significance by effect size between survival and homocysteine level and significance by effect size between survival and tumor location were calculated.

Results: Cohort included 65.6% men and 34.4% women (age 19-81 years). The mean value of Hcys was 63 times higher than the physiological maximum limit and 8 times higher than in severe hyperhomocysteinemia. Patients with tumor with deep localization had higher Hcys than rGB with lobar tumor. Patients with ≤ 585 μM survived longer than ≥ 585 μM. Patients with right hemisphere tumor localization survived longer than left hemisphere tumor localization.

Conclusions: The results confirm that Hcys may be an indicator of the highly proliferative characteristic and heterogeneity of the methyl group pathway in the different brain microenvironments in rGBM related to distinct microenvironments with marked metabolic demand.