A strategy for multimodal integration of transcriptomics, proteomics, and radiomics data for the prediction of recurrence in patients with IDH-mutant gliomas.

Journal: International journal of cancer
Published Date:

Abstract

Isocitrate dehydrogenase-mutant gliomas are lethal brain cancers that impair quality of life in young adults. Although less aggressive than glioblastomas, IDH-mutant gliomas invariably progress to incurable disease with unpredictable recurrence. A better classification of patient risk of recurrence is needed. Here, we describe a multimodal analytical pipeline integrating imaging, transcriptomic, and proteomic profiles using machine learning to improve patient stratification with novel signatures of patient risk of recurrence based on gene expression, protein level, and imaging. Additionally, we describe the biological characteristics of IDH-mutant glioma subtypes categorized by positron emission tomography (PET) and histology, and we reinforce the integration of positron emission tomography (PET) metrics in the classification of IDH-mutant gliomas. We identify a gene signature (KRT19, RUNX3, and SCRT2) and a protein signature (ATXN10, EIF4H, ITGAV, and NCAM1) associated with an increased risk of early recurrence. Furthermore, we integrated these markers with imaging-derived features, obtaining a better stratification of IDH-mutant glioma patients in comparison to histomolecular classification alone.

Authors

  • Tiffanie Chouleur
    INSERM U1312 BRIC, University of Bordeaux, Pessac, France.
  • Christèle Etchegaray
    INRIA, University of Bordeaux Inria Monc, IMB, UMR 5251, Talence, France.
  • Laura Villain
    INSERM Bordeaux Population Health Research Center, SISTM team, UMR 1219, University of Bordeaux, Bordeaux, France.
  • Antoine Lesur
    Luxembourg Institute of Health, Strassen, Luxembourg.
  • Thomas Ferté
    Bordeaux Hospital University Center, Pôle de santé publique, Service d'information médicale, Unité Informatique et Archivistique Médicales, F-33000 Bordeaux, France; Univ. Bordeaux ISPED, Inserm Bordeaux Population Health Research Center UMR 1219, Inria BSO, team SISTM, F-33000 Bordeaux, France. Electronic address: thomas.ferte@u-bordeaux.fr.
  • Marco Rossi
    Neurosurgical Oncology Unit, Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy.
  • Laetitia Andrique
    INSERM U1312 BRIC, University of Bordeaux, Pessac, France.
  • Costanza Simoncini
    INRIA, University of Bordeaux Inria Monc, IMB, UMR 5251, Talence, France.
  • Anne-Sophie Giacobbi
    Laboratoire de Biologie Computationnelle et Quantitative (LCQB), UMR 7238 CNRS, Université Sorbonne, Paris, France.
  • Matteo Gambaretti
    Department of Oncology and Hemato-Oncology, Neurosurgical Oncology Unit, Università degli Studi di Milano and IRCCS Galeazzi Sant'Ambrogio, Milano, Italy.
  • Egesta Lopci
  • Bethania Fernades
    Pathology Unit, Humanitas Research Hospital, Milano, Italy.
  • Gunnar Dittmar
    Luxembourg Institute of Health, Strassen, Luxembourg.
  • Rolf Bjerkvig
    Department of Biomedicine and KG Jebsen Brain Tumor Research Center, University of Bergen, Bergen, Norway.
  • Boris Hejblum
    INSERM Bordeaux Population Health Research Center, SISTM team, UMR 1219, University of Bordeaux, Bordeaux, France.
  • Rodolphe Thiébaut
    ISPED, USMR, CHU de Bordeaux, France.
  • Olivier Saut
    INRIA Bordeaux Sud-Ouest, France.
  • Lorenzo Bello
    Department of Oncology and Hematology-Oncology, Universitá degli Studi di Milano, Milan, Italy.
  • Andreas Bikfalvi
    INSERM U1312 BRIC, University of Bordeaux, Pessac, France.