Lipidomic-Based Approach to 10 s Classification of Major Pediatric Brain Cancer Types with Picosecond Infrared Laser Mass Spectrometry.

Jan 29, 2024

Experts: Michael Woolman,Taira Kiyota,Siham A Belgadi,Naohide Fujita,Alexa Fiorante,Vijay Ramaswamy,Craig Daniels,James T Rutka,Chris McIntosh,David G Munoz,Howard J Ginsberg,Ahmed Aman,Arash Zarrine-Afsar

Picosecond infrared laser mass spectrometry (PIRL-MS) is shown, through a retrospective patient tissue study, to differentiate medulloblastoma cancers from pilocytic astrocytoma and two molecular subtypes of ependymoma (PF-EPN-A, ST-EPN-RELA) using laser-extracted lipids profiled with PIRL-MS in 10 s of sampling and analysis time. The average sensitivity and specificity values for this classification, taking genomic profiling data as standard, were 96.41 and 99.54%, and this classification used many molecular features resolvable in 10 s PIRL-MS spectra. Data analysis and liquid chromatography coupled with tandem high-resolution mass spectrometry (LC-MS/MS) further allowed us to reduce the molecular feature list to only 18 metabolic lipid markers most strongly involved in this classification. The identified ‘metabolite array’ was comprised of a variety of phosphatidic and fatty acids, ceramides, and phosphatidylcholine/ethanolamine and could mediate the above-mentioned classification with average sensitivity and specificity values of 94.39 and 98.78%, respectively, at a 95% confidence in prediction probability threshold. Therefore, a rapid and accurate pathology classification of select pediatric brain cancer types from 10 s PIRL-MS analysis using known metabolic biomarkers can now be available to the neurosurgeon. Based on retrospective mining of ‘survival’ versus ‘extent-of-resection’ data, we further identified pediatric cancer types that may benefit from actionable 10 s PIRL-MS pathology feedback. In such cases, aggressiveness of the surgical resection can be optimized in a manner that is expected to benefit the patient’s overall or progression-free survival. PIRL-MS is a promising tool to drive such personalized decision-making in the operating theater.

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ABOUT THE EXPERTS

Michael Woolman,Taira Kiyota,Siham A Belgadi,Naohide Fujita,Alexa Fiorante,Vijay Ramaswamy,Craig Daniels,James T Rutka,Chris McIntosh,David G Munoz,Howard J Ginsberg,Ahmed Aman,Arash Zarrine-Afsar

Michael Woolman

Princess Margaret Cancer Centre, University Health Network, 101 College Street, Toronto, Ontario M5G 1L7, Canada.

Department of Medical Biophysics, University of Toronto, 101 College Street, Toronto, Ontario M5G 1L7, Canada.

Taira Kiyota

Ontario Institute for Cancer Research (OICR), 661 University Ave Suite 510, Toronto, Ontario M5G 0A3, Canada.

Siham A Belgadi

Department of Medical Biophysics, University of Toronto, 101 College Street, Toronto, Ontario M5G 1L7, Canada.

Naohide Fujita

Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, 686 Bay Street, Toronto, Ontario M5G 0A4, Canada.

Alexa Fiorante

Princess Margaret Cancer Centre, University Health Network, 101 College Street, Toronto, Ontario M5G 1L7, Canada.

Department of Medical Biophysics, University of Toronto, 101 College Street, Toronto, Ontario M5G 1L7, Canada.

Vijay Ramaswamy

Department of Medical Biophysics, University of Toronto, 101 College Street, Toronto, Ontario M5G 1L7, Canada.

Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, 686 Bay Street, Toronto, Ontario M5G 0A4, Canada.

Craig Daniels

Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, 686 Bay Street, Toronto, Ontario M5G 0A4, Canada.

James T Rutka

Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, 686 Bay Street, Toronto, Ontario M5G 0A4, Canada.

Department of Surgery, University of Toronto, 149 College Street, Toronto, Ontario M5T 1P5, Canada.

Chris McIntosh

Toronto General Hospital Research Institute, University Health Network, 200 Elizabeth Street, Toronto, Ontario M5G-2C4, Canada.

David G Munoz

Keenan Research Center for Biomedical Science & the Li Ka Shing Knowledge Institute, St. Michael’s Hospital, 30 Bond Street, Toronto, Ontario M5B 1W8, Canada.

Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King’s College Circle, Sixth Floor, Toronto,Ontario M5S 1A8, Canada.

Howard J Ginsberg

Department of Surgery, University of Toronto, 149 College Street, Toronto, Ontario M5T 1P5, Canada.

Keenan Research Center for Biomedical Science & the Li Ka Shing Knowledge Institute, St. Michael’s Hospital, 30 Bond Street, Toronto, Ontario M5B 1W8, Canada.

Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King’s College Circle, Sixth Floor, Toronto,Ontario M5S 1A8, Canada.

Ahmed Aman

Ontario Institute for Cancer Research (OICR), 661 University Ave Suite 510, Toronto, Ontario M5G 0A3, Canada.

Leslie Dan, Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, Ontario M5S 3M2, Canada.

Arash Zarrine-Afsar

Princess Margaret Cancer Centre, University Health Network, 101 College Street, Toronto, Ontario M5G 1L7, Canada.

Department of Medical Biophysics, University of Toronto, 101 College Street, Toronto, Ontario M5G 1L7, Canada.

Department of Surgery, University of Toronto, 149 College Street, Toronto, Ontario M5T 1P5, Canada.

Keenan Research Center for Biomedical Science & the Li Ka Shing Knowledge Institute, St. Michael’s Hospital, 30 Bond Street, Toronto, Ontario M5B 1W8, Canada.