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© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Simple Summary

Characterization of immunophenotypes in GBM is important for therapeutic stratification and helps predict treatment response and prognosis. However, identifying immunophenotypes of patients with GBM requires multiple laboratory experiments and is time consuming. We developed a non-invasive method to evaluate enrichment levels of CTL, aDC, Treg, and MDSC immune cells to classify immunophenotypes of GBM tumor microenvironment with radiomic features of MR imaging. Five immunophenotypes (G1–G5) of GBM can be classified with specific gene set enrichment analysis. G2 had the worst prognosis and comprised highly enriched MDSCs and lowly enriched CTLs. G3 had the best prognosis and comprised lowly enriched MDSCs and Tregs and highly enriched CTLs. Moreover, the developed radiomics models can successfully identified these two groups by immune cell subsets enriched levels prediction. Therefore, it is possible to characterize immunophenotypes of GBM and predict patient prognosis with radiomics methods.

Abstract

Characterization of immunophenotypes in glioblastoma (GBM) is important for therapeutic stratification and helps predict treatment response and prognosis. Radiomics can be used to predict molecular subtypes and gene expression levels. However, whether radiomics aids immunophenotyping prediction is still unknown. In this study, to classify immunophenotypes in patients with GBM, we developed machine learning-based magnetic resonance (MR) radiomic models to evaluate the enrichment levels of four immune subsets: Cytotoxic T lymphocytes (CTLs), activated dendritic cells, regulatory T cells (Tregs), and myeloid-derived suppressor cells (MDSCs). Independent testing data and the leave-one-out cross-validation method were used to evaluate model effectiveness and model performance, respectively. We identified five immunophenotypes (G1 to G5) based on the enrichment level for the four immune subsets. G2 had the worst prognosis and comprised highly enriched MDSCs and lowly enriched CTLs. G3 had the best prognosis and comprised lowly enriched MDSCs and Tregs and highly enriched CTLs. The average accuracy of T1-weighted contrasted MR radiomics models of the enrichment level for the four immune subsets reached 79% and predicted G2, G3, and the “immune-cold” phenotype (G1) according to our radiomics models. Our radiomic immunophenotyping models feasibly characterize the immunophenotypes of GBM and can predict patient prognosis.

Details

Title
Radiomic Immunophenotyping of GSEA-Assessed Immunophenotypes of Glioblastoma and Its Implications for Prognosis: A Feasibility Study
Author
Hsu, Justin Bo-Kai 1   VIAFID ORCID Logo  ; Gilbert Aaron Lee 1 ; Chang, Tzu-Hao 2   VIAFID ORCID Logo  ; Shiu-Wen, Huang 3 ; Nguyen Quoc Khanh Le 4   VIAFID ORCID Logo  ; Chen, Yung-Chieh 5 ; Duen-Pang Kuo 5 ; Yi-Tien, Li 6   VIAFID ORCID Logo  ; Cheng-Yu, Chen 7 

 Department of Medical Research, Taipei Medical University Hospital, Taipei 110, Taiwan; [email protected] (J.B.-K.H.); [email protected] (G.A.L.); [email protected] (S.-W.H.); Translational Imaging Research Center, Taipei Medical University Hospital, Taipei 110, Taiwan; [email protected] (Y.-C.C.); [email protected] (D.-P.K.); [email protected] (Y.-T.L.) 
 Graduate Institute of Biomedical Informatics, Taipei Medical University, Taipei 110, Taiwan; [email protected]; Clinical Big Data Research Center, Taipei Medical University Hospital, Taipei 110, Taiwan 
 Department of Medical Research, Taipei Medical University Hospital, Taipei 110, Taiwan; [email protected] (J.B.-K.H.); [email protected] (G.A.L.); [email protected] (S.-W.H.); Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan 
 Professional Master Program in Artificial Intelligence in Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; [email protected]; Research Center for Artificial Intelligence in Medicine, Taipei Medical University, Taipei 110, Taiwan 
 Translational Imaging Research Center, Taipei Medical University Hospital, Taipei 110, Taiwan; [email protected] (Y.-C.C.); [email protected] (D.-P.K.); [email protected] (Y.-T.L.); Department of Medical Imaging, Taipei Medical University Hospital, Taipei 110, Taiwan 
 Translational Imaging Research Center, Taipei Medical University Hospital, Taipei 110, Taiwan; [email protected] (Y.-C.C.); [email protected] (D.-P.K.); [email protected] (Y.-T.L.); Neuroscience Research Center, Taipei Medical University, Taipei 110, Taiwan 
 Translational Imaging Research Center, Taipei Medical University Hospital, Taipei 110, Taiwan; [email protected] (Y.-C.C.); [email protected] (D.-P.K.); [email protected] (Y.-T.L.); Professional Master Program in Artificial Intelligence in Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; [email protected]; Research Center for Artificial Intelligence in Medicine, Taipei Medical University, Taipei 110, Taiwan; Department of Medical Imaging, Taipei Medical University Hospital, Taipei 110, Taiwan; Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan 
First page
3039
Publication year
2020
Publication date
2020
Publisher
MDPI AG
e-ISSN
20726694
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2547630448
Copyright
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.