Profiling of Carnitine Shuttle System Intermediates in Gliomas Using Solid-Phase Microextraction (SPME).

Joanna Bogusiewicz,Marcin Birski,Krzysztof Gorynski,Dariusz Paczkowski,Paulina Zofia Gorynska,Barbara Bojko,Marek Harat,Katarzyna Burlikowska,Jacek Furtak,Karol Jaroch

doi:10.3390/molecules26206112

Abstract

Alterations in the carnitine shuttle system may be an indication of the presence of cancer. As such, in-depth analyses of this pathway in different malignant tumors could be important for the detection and treatment of this disease. The current study aims to assess the profiles of carnitine and acylcarnitines in gliomas with respect to their grade, the presence of isocitrate dehydrogenase (IDH) mutations, and 1p/19q co-deletion. Brain tumors obtained from 19 patients were sampled on-site using solid-phase microextraction (SPME) immediately following excision. Analytes were desorbed and then analyzed via liquid chromatography–high-resolution mass spectrometry. The results showed that SPME enabled the extraction of carnitine and 22 acylcarnitines. An analysis of the correlation factor revealed the presence of two separate clusters: short-chain and long-chain carnitine esters. Slightly higher carnitine and acylcarnitine concentrations were observed in the higher-malignancy tumor samples (high vs. low grade) and in those samples with worse projected clinical outcomes (without vs. with IDH mutation; without vs. with 1p/19q co-deletion). Thus, the proposed chemical biopsy approach offers a simple solution for on-site sampling that enables sample preservation, thus supporting comprehensive multi-method analyses.

Highlights

Introduction published maps and institutional affilGliomas are among the most dangerous and insidious brain tumors due to their high heterogeneity and the late manifestation of a wide range of non-specific symptoms, such as seizures, headaches, nausea, dizziness, fatigue, vision problems, and numbness [1,2,3,4,5].Delayed diagnosis favors tumor progression and leads to worse prognoses and, a rapid decrease in the patient’s quality of life
This study aims to develop a more in-depth understanding of the intermediates in a carnitine shuttle system using data acquired from untargeted lipidomic analyses of brain tumors via solid-phase microextraction (SPME)–LC–MS, with particular consideration given to tumor grade, the presence of isocitrate dehydrogenase (IDH) mutation, and 1p/19q codeletion
SPME extraction from intact tissue did not cause any damage to the collected tumor, which precluded further performance of routine tests, i.e., histological or genotyping

Summary

Introduction

Gliomas are among the most dangerous and insidious brain tumors due to their high heterogeneity and the late manifestation of a wide range of non-specific symptoms, such as seizures, headaches, nausea, dizziness, fatigue, vision problems, and numbness [1,2,3,4,5]. Delayed diagnosis favors tumor progression and leads to worse prognoses and, a rapid decrease in the patient’s quality of life. The introduction of accurate medical interventions, which often combine neurosurgery and chemo- or radiotherapy, is necessary. Genetic testing—for example, those that analyze the status of O6-methylguanineDNA methyltransferase (MGMT) methylation, the presence of IDH mutation, or 1p/19q co-deletion—serves as a complement to the diagnosis process and enables accurate clinical prognoses [2,5]. The survival rate of glioma patients is still low due to a lack of iations

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