Abstract
Among mediators of oxidative stress, highly reactive secondary aldehydic lipid peroxidation products can initiate the processes of spontaneous mutagenesis and carcinogenesis and can also act as a growth-regulating factors and signaling molecules. We explored whether these aldehydes and histone H3 mRNA levels could serve as biomarkers of malignancy and predictive factor in human brain astrocytomas. Histone H3 mRNA, a biomarker of cellular proliferation, was analyzed by QRT-PCR (TaqMan). Aldehydic lipid peroxidation products were determined as their dinitrophenylhydrazone derivatives in specimens obtained from 26 adult patients with brain astrocytomas. RP-HPLC with diode array detector and MSMS spectrometer were used for the analysis. H3 mRNA, 2-hydroxyhexanal, and 4-hydroxynonenal levels were higher in high-grade astrocytomas compared to low-grade astrocytomas and showed negative correlation with survival. Higher levels of 2-hydroxyhexanal and 4-hydroxynonenal, and lower levels of n-hexanal were associated with poorer patient prognosis. Our data suggest that tissue concentrations of aldehydic lipid peroxidation products can assist grading and predicting the clinical outcome in patients with astrocytic brain tumors. Possibly, this parameter will enhance optimal selection of patients for individualized treatment protocols, tailored to unique biochemical and molecular profile of the tumor.
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