Use of MRI, metabolomic, and genomic biomarkers to identify mechanisms of chemoresistance in glioma

Levenson, Cathy W.; Morgan, Thomas J.; Twigg, Pamela D.; Logan, Timothy M.; Schepkin, Victor D.

doi:10.20517/cdr.2019.18

Cited by 2 publications

(1 citation statement)

References 86 publications

(109 reference statements)

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“…Tissue-specific energy metabolism dysfunction was not observed at the system level compared with the previous study. [ 62 ] Given the small sample size of this study, which is the most important limitation of our study, a larger patient cohort needs to be included in future studies to test the accuracy of other metabolites for phenotyping. Due to the extremely limited quantitative ability of untargeted metabolomics techniques, a targeted metabolomics experiment is required for further investigation.…”

Section: Discussionmentioning

confidence: 99%

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

Du¹,

Huang²,

Wei³

et al. 2022

Medicine

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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. Abbreviations: AA = anaplastic astrocytoma, ALALA = α-linolenic acid and linoleic acid, AUC = area under the curve, DOS = degradation of superoxide, ESI = electrospray Ionization, HC = healthy Control, HMDB = human metabolites database, IDH = isocitrate dehydrogenase, KEGG = Kyoto Encyclopedia of Genes and Genomes, METC = mitochondrial electron transport chain, MGMT = methylguanine-DNA methyltransferase, MT = mutant type, NOS = not otherwise specified, OPLS-DA = orthogonal projections to latent structures-discriminant analysis, PC = phosphocholine, PCA = principal component analysis, PE = phosphoethanolamine, QC = quality control, THS = thyroid hormone synthesis, UPLC-Q/TOF-MS = liquid chromatography-quadrupole/time-of-flight-mass spectrometry, WT = wide type.

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Section: Discussionmentioning

confidence: 99%

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

Du¹,

Huang²,

Wei³

et al. 2022

Medicine

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Intraoperative computed tomography perfusion navigation for maximal resection of high grade gliomas: a prospective non-randomized trial

Talybov,

Trofimova,

Mochalov

et al. 2023

Almanac of Clinical Medicine

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Background: The main purpose of surgery for glioblastoma is to ensure the maximally possible cytoreduction. Computed tomography perfusion imaging has non-invasive tools for assessment of tumor blood flow and allows for visualization of the tumor borders and its most malignant zones. Aim: To evaluate the efficacy of intraoperative computed tomography perfusion navigation (ICTPN) during surgery for high grade gliomas. Materials and methods: This prospective non-randomized study included 142 patients (76 men and 66 women) with morphologically verified diagnosis of glioblastoma or diffuse astrocytoma grade 4 (World Health Organization 2021 criteria), who had surgery from 2016 to 2022. The ICTPN-based procedures were performed in 94 patients, with 55 with gross total and 39 with subtotal tumor resection. The control group included 48 patients with non-ICTPN-based surgical procedures. All patients were treated with standard adjuvant chemoradiation therapy. The efficacy of surgery was assessed every 3 months. The study endpoint was any tumor progression. The duration of the follow-up was 15 months. Baseline and contrast-enhanced preoperative imaging and postoperative follow-up assessments were performed with a 3T magnetic resonance imaging scanner (General Electric Discovery W750). ICTPN was done with a 32 slice computed tomography scanner (Toshiba Aquilion LB). Results: In the totally resected ICTPN group, the mean duration of the relapse-free period was 13.05 months; the relapse-free survival at 6 and 12 months was 92 and 55%, respectively (p 0.001). These results were significantly better than those in the subtotally resected ICTPN patients (8.98 months, 66 and 9%, respectively; log rank test for Kaplan-Meier curves, p 0.001) and in non-ICTPN patients (5.81 months, 23 and 0%, respectively, log rank test, p 0.001). Conclusion: ICTPN enables a more objective assessment of the tumor borders and the extent of its resection, as well as relapse-free survival benefits for the patients.

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Use of MRI, metabolomic, and genomic biomarkers to identify mechanisms of chemoresistance in glioma

Cited by 2 publications

References 86 publications

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

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

Intraoperative computed tomography perfusion navigation for maximal resection of high grade gliomas: a prospective non-randomized trial

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