Comprehensive metabolomics study on the pathogenesis of anaplastic astrocytoma via UPLC-Q/TOF-MS

Abstract

Anaplastic astrocytoma (AA) is a malignant carcinoma whose pathogenesis remains to be fully elucidated. System biology techniques have been widely used to clarify the mechanism of diseases from a systematic perspective.

The present study aimed to explore the pathogenesis and novel potential biomarkers for the diagnosis of AA according to metabolic differences. Patients with AA (n = 12) and healthy controls (n = 15) were recruited. Serum was assayed with untargeted ultraperformance liquid chromatography-quadrupole/time-of-flight-mass spectrometry (UPLC-Q/TOF-MS) metabolomic techniques. The data were further evaluated using multivariate analysis and bioinformatic methods based on the KEGG database to determine the distinct metabolites and perturbed pathways.

Principal component analysis and orthogonal projections to latent structures-discriminant analysis (OPLS-DA) identified the significance of the distinct metabolic pattern between patients with AA and healthy controls ( P < .001) in both ESI modes. Permutation testing confirmed the validity of the OPLS-DA model (permutation = 200, Q2 < 0.5). In total, 24 differentiated metabolites and 5 metabolic pathways, including sphingolipid, glycerophospholipid, caffeine, linoleic acid, and porphyrin metabolism, were identified based on the OPLS-DA model. 3-Methylxanthine, sphinganine, LysoPC(18:1), and lactosylceramide were recognized as potential biomarkers with excellent sensitivity and specificity (area under the curve > 98%).

These findings indicate that the perturbed metabolic pattern related to immune regulation and cellular signal transduction is associated with the pathogenesis of AA. 3-Methylxanthine, sphinganine, LysoPC(18:1), and lactosylceramide could be used as biomarkers of AA in future clinical practice. This study provides a therapeutic basis for further studies on the mechanism and precise clinical diagnosis of AA.