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Article

Interrogation of IDH1 Status in Gliomas by Fourier Transform Infrared Spectroscopy

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WestCHEM, Department of Pure and Applied Chemistry, Technology and Innovation Centre, University of Strathclyde, 99 George St., Glasgow G1 1RD, UK
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ClinSpec Diagnostics, Technology and Innovation Centre, University of Strathclyde, 99 George St., Glasgow G1 1RD, UK
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Department of Clinical Neurosciences, Translational Neurosurgery, Western General Hospital, Edinburgh EH4 2XU, UK
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Institute of Systems, Molecular and Integrated Biology, University of Liverpool & The Walton Centre NHS Foundation Trust, Lower Lane, Fazakerley, Liverpool L9 7LJ, UK
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Institute of Genetics and Molecular Medicine, University of Edinburgh, Division of Pathology, Western General Hospital, Crewe Road South, Edinburgh EH4 2XR, UK
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Diamond Light Source, Harwell Science and Innovation Campus, Chilton, Oxfordshire OX11 0DE, UK
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Walton Research Tissue Bank, Neurosciences Laboratories, The Walton Centre NHS Foundation Trust, Lower Lane, Fazakerley, Liverpool L9 7LJ, UK
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WestCHEM, Department of Pure and Applied Chemistry, Thomas Graham Building, University of Strathclyde, 295 Cathedral Str., Glasgow G1 1XL, UK
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Author to whom correspondence should be addressed.
Cancers 2020, 12(12), 3682; https://doi.org/10.3390/cancers12123682
Received: 23 October 2020 / Revised: 23 November 2020 / Accepted: 4 December 2020 / Published: 8 December 2020
Gliomas represent the vast majority of primary brain tumours and are of significant medical importance due to the poor clinical course of affected patients. The isocitrate dehydrogenase 1 (IDH1) mutation is associated with improved prognosis, compared to patients with IDH1-wildtype lesions of the same stage. In this proof-of-concept study, Fourier transform infrared spectroscopy was used to determine the IDH1 molecular status in fixed glioma sections. Classification algorithms successfully distinguished the two IDH1 classes with high accuracies (>80%). Knowledge of the IDH1 status would be beneficial, as maximum resection may be preferred in patients with IDH1-mutant gliomas, whilst a more limited resection can be best for IDH1-wildtype gliomas. Furthermore, we examined blood serum in an attempt to identify the biomolecular alterations caused by the IDH1 mutation. Non-invasive approaches that can detect the molecular status may guide some patients to an alternative treatment prior to surgery.
Mutations in the isocitrate dehydrogenase 1 (IDH1) gene are found in a high proportion of diffuse gliomas. The presence of the IDH1 mutation is a valuable diagnostic, prognostic and predictive biomarker for the management of patients with glial tumours. Techniques involving vibrational spectroscopy, e.g., Fourier transform infrared (FTIR) spectroscopy, have previously demonstrated analytical capabilities for cancer detection, and have the potential to contribute to diagnostics. The implementation of FTIR microspectroscopy during surgical biopsy could present a fast, label-free method for molecular genetic classification. For example, the rapid determination of IDH1 status in a patient with a glioma diagnosis could inform intra-operative decision-making between alternative surgical strategies. In this study, we utilized synchrotron-based FTIR microanalysis to probe tissue microarray sections from 79 glioma patients, and distinguished the positive class (IDH1-mutated) from the IDH1-wildtype glioma, with a sensitivity and specificity of 82.4% and 83.4%, respectively. We also examined the ability of attenuated total reflection (ATR)-FTIR spectroscopy in detecting the biomolecular events and global epigenetic and metabolic changes associated with mutations in the IDH1 enzyme, in blood serum samples collected from an additional 72 brain tumour patients. Centrifugal filtration enhanced the diagnostic ability of the classification models, with balanced accuracies up to ~69%. Identification of the molecular status from blood serum prior to biopsy could further direct some patients to alternative treatment strategies. View Full-Text
Keywords: biophotonics; infrared; imaging; cancer; histopathology; biofluids; glioma biophotonics; infrared; imaging; cancer; histopathology; biofluids; glioma
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MDPI and ACS Style

Cameron, J.M.; Conn, J.J.A.; Rinaldi, C.; Sala, A.; Brennan, P.M.; Jenkinson, M.D.; Caldwell, H.; Cinque, G.; Syed, K.; Butler, H.J.; Hegarty, M.G.; Palmer, D.S.; Baker, M.J. Interrogation of IDH1 Status in Gliomas by Fourier Transform Infrared Spectroscopy. Cancers 2020, 12, 3682. https://doi.org/10.3390/cancers12123682

AMA Style

Cameron JM, Conn JJA, Rinaldi C, Sala A, Brennan PM, Jenkinson MD, Caldwell H, Cinque G, Syed K, Butler HJ, Hegarty MG, Palmer DS, Baker MJ. Interrogation of IDH1 Status in Gliomas by Fourier Transform Infrared Spectroscopy. Cancers. 2020; 12(12):3682. https://doi.org/10.3390/cancers12123682

Chicago/Turabian Style

Cameron, James M., Justin J.A. Conn, Christopher Rinaldi, Alexandra Sala, Paul M. Brennan, Michael D. Jenkinson, Helen Caldwell, Gianfelice Cinque, Khaja Syed, Holly J. Butler, Mark G. Hegarty, David S. Palmer, and Matthew J. Baker 2020. "Interrogation of IDH1 Status in Gliomas by Fourier Transform Infrared Spectroscopy" Cancers 12, no. 12: 3682. https://doi.org/10.3390/cancers12123682

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