Spatial habitats from multiparametric MR imaging are associated with signaling pathway activities and survival in glioblastoma
| Autor: | Shivali Narang, Donnie Kim, Anita Rao, Michelle M. Kim, Sunil Krishnan, Ganesh Rao, Salmaan Ahmed, Katherine Dextraze, Abhijoy Saha, Arvind Rao, Saphal Narang, Michael Lehrer, Dinesh S. Rao, Venkatesh Madhugiri, Clifton D. Fuller |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
signaling pathway activity
medicine.diagnostic_test Genetic heterogeneity glioblastoma Magnetic resonance imaging Dirichlet regression Computational biology Fluid-attenuated inversion recovery Biology imaging-genomics analysis medicine.disease Phenotype Regression 030218 nuclear medicine & medical imaging 03 medical and health sciences 0302 clinical medicine Oncology 030220 oncology & carcinogenesis image-derived spatial habitat medicine Clinical significance Signal transduction Glioblastoma Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | Glioblastoma (GBM) show significant inter- and intra-tumoral heterogeneity, impacting response to treatment and overall survival time of 12-15 months. To study glioblastoma phenotypic heterogeneity, multi-parametric magnetic resonance images (MRI) of 85 glioblastoma patients from The Cancer Genome Atlas were analyzed to characterize tumor-derived spatial habitats for their relationship with outcome (overall survival) and to identify their molecular correlates (i.e., determine associated tumor signaling pathways correlated with imaging-derived habitat measurements). Tumor sub-regions based on four sequences (fluid attenuated inversion recovery, T1-weighted, post-contrast T1-weighted, and T2-weighted) were defined by automated segmentation. From relative intensity of pixels in the 3-dimensional tumor region, "imaging habitats" were identified and analyzed for their association to clinical and genetic data using survival modeling and Dirichlet regression, respectively. Sixteen distinct tumor sub-regions ("spatial imaging habitats") were derived, and those associated with overall survival (denoted "relevant" habitats) in glioblastoma patients were identified. Dirichlet regression implicated each relevant habitat with unique pathway alterations. Relevant habitats also had some pathways and cellular processes in common, including phosphorylation of STAT-1 and natural killer cell activity, consistent with cancer hallmarks. This work revealed clinical relevance of MRI-derived spatial habitats and their relationship with oncogenic molecular mechanisms in patients with GBM. Characterizing the associations between imaging-derived phenotypic measurements with the genomic and molecular characteristics of tumors can enable insights into tumor biology, further enabling the practice of personalized cancer treatment. The analytical framework and workflow demonstrated in this study are inherently scalable to multiple MR sequences. |
| Databáze: | OpenAIRE |
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