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Interrogation of IDH1 status in gliomas by fourier transform infrared spectroscopy

DOI: 10.3390/cancers12123682 DOI Help

Authors: James M. Cameron (University of Strathclyde) , Justin J. A. Conn (University of Strathclyde) , Christopher Rinaldi (University of Strathclyde) , Alexandra Sala (University of Strathclyde) , Paul M. Brennan (Western General Hospital) , Michael D. Jenkinson (University of Liverpool; The Walton Centre NHS Foundation Trust) , Helen Caldwell (University of Edinburgh; Western General Hospital) , Gianfelice Cinque (Diamond Light Source) , Khaja Syed (The Walton Centre NHS Foundation Trust) , Holly J. Butler (University of Strathclyde) , Mark G. Hegarty (University of Strathclyde) , David S. Palmer (University of Strathclyde) , Matthew J. Baker (University of Strathclyde)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Cancers , VOL 12

State: Published (Approved)
Published: December 2020
Diamond Proposal Number(s): 23417

Open Access Open Access

Abstract: 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.

Subject Areas: Biology and Bio-materials


Instruments: B22-Multimode InfraRed imaging And Microspectroscopy

Documents:
cancers-12-03682.pdf