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Deep learning features from diffusion tensor imaging improve glioma stratification and identify risk groups with distinct molecular pathway activities.

Department of MRI, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Glioma Multidisciplinary Research Group, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China. Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. Glioma Multidisciplinary Research Group, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. Department of MRI, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. Department of Medical Imaging, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. Electronic address: lvxf@sysucc.org.cn. Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China; National Innovation Center for Advanced Medical Devices, Shenzhen, China. Electronic address: zc.li@siat.ac.cn. Glioma Multidisciplinary Research Group, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. Electronic address: fcczhangzy1@zzu.edu.cn.

EBioMedicine. 2021;:103583
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Abstract

BACKGROUND To develop and validate a deep learning signature (DLS) from diffusion tensor imaging (DTI) for predicting overall survival in patients with infiltrative gliomas, and to investigate the biological pathways underlying the developed DLS. METHODS The DLS was developed based on a deep learning cohort (n = 688). The key pathways underlying the DLS were identified on a radiogenomics cohort with paired DTI and RNA-seq data (n=78), where the prognostic value of the pathway genes was validated in public databases (TCGA, n = 663; CGGA, n = 657). FINDINGS The DLS was associated with survival (log-rank P < 0.001) and was an independent predictor (P < 0.001). Incorporating the DLS into existing risk system resulted in a deep learning nomogram predicting survival better than either the DLS or the clinicomolecular nomogram alone, with a better calibration and classification accuracy (net reclassification improvement 0.646, P < 0.001). Five kinds of pathways (synaptic transmission, calcium signaling, glutamate secretion, axon guidance, and glioma pathways) were significantly correlated with the DLS. Average expression value of pathway genes showed prognostic significance in our radiogenomics cohort and TCGA/CGGA cohorts (log-rank P < 0.05). INTERPRETATION DTI-derived DLS can improve glioma stratification by identifying risk groups with dysregulated biological pathways that contributed to survival outcomes. Therapies inhibiting neuron-to-brain tumor synaptic communication may be more effective in high-risk glioma defined by DTI-derived DLS. FUNDING A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

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Publication Type : Clinical Trial

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