TY - JOUR
T1 - Spatial habitats from multiparametric MR imaging are associated with signaling pathway activities and survival in glioblastoma
AU - Dextraze, Katherine
AU - Saha, Abhijoy
AU - Kim, Donnie
AU - Narang, Shivali
AU - Lehrer, Michael
AU - Rao, Anita
AU - Narang, Saphal
AU - Rao, Dinesh
AU - Ahmed, Salmaan
AU - Madhugiri, Venkatesh
AU - Fuller, Clifton David
AU - Kim, Michelle M.
AU - Krishnan, Sunil
AU - Rao, Ganesh
AU - Rao, Arvind
N1 - Publisher Copyright:
© Dextraze et al.
PY - 2017
Y1 - 2017
N2 - 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 imagingderived 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.
AB - 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 imagingderived 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.
KW - Dirichlet regression
KW - Glioblastoma
KW - Image-derived spatial habitat
KW - Imaging-genomics analysis
KW - Signaling pathway activity
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U2 - 10.18632/oncotarget.22947
DO - 10.18632/oncotarget.22947
M3 - Article
C2 - 29348883
AN - SCOPUS:85038843551
SN - 1949-2553
VL - 8
SP - 112992
EP - 113001
JO - Oncotarget
JF - Oncotarget
IS - 68
ER -