Identification of Malignant Progression of Gliomas through Metabolomics of Cerebrospinal Fluid and Serum

Abstract

Gliomas are the most common malignant primary intracranial tumors. The survival period of patients with recurrent gliomas is significantly shortened further. There is an urgent need for a method with higher sensitivity and specificity to distinguish between primary, recurrent, and radiation-injury gliomas. This study involved a comprehensive metabolomics analysis using liquid chromatography–mass spectrometry (LC–MS) on cerebrospinal fluid (CSF) and serum samples from 124 patients diagnosed with gliomas via surgical resection or biopsy. Samples were categorized into primary, recurrent, and radiation injury (RI) groups. Metabolomics differences in CSF and serum were proven among the three groups. Compared with the primary gliomas, recurrent gliomas showed a higher level of 2-deoxyribose 5-phosphate (dRP) in the CSF, which further confirmed that recurrence of glioma may be linked to the rate-limiting step of DNA base excision repair (BER)─the removal of dRP. Additionally, higher serum hypoxanthine levels in patients with RI indicate that hypoxanthine concentration and hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activity may serve as indicators of glioma sensitivity to radiotherapy. The study also highlighted ornithine and its related metabolites as potential key indicators to differentiate between glioma recurrence and radiation injury. These findings suggest potential new avenues for the diagnosis and treatment of gliomas.