Radiogenomic Analysis of Breast Cancer by Linking MRI Phenotypes with Tumor Gene Expression.

Autor: Bismeijer T; From the Division of Molecular Carcinogenesis, Oncode Institute (T.B., S.C., L.F.A.W.), Division of Molecular Pathology (S.C., E.H.L., J.W.), Department of Radiology (C.E.L.), and Department of Pathology (J.W.), the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; Image Sciences Institute, University Medical Center Utrecht, Utrecht, the Netherlands (B.H.M.v.d.V., M.A.V., K.G.A.G.); and Faculty of Electrical Engineering, Mathematics, and Computer Science, Delft University of Technology, Delft, the Netherlands (L.F.A.W.)., van der Velden BHM; From the Division of Molecular Carcinogenesis, Oncode Institute (T.B., S.C., L.F.A.W.), Division of Molecular Pathology (S.C., E.H.L., J.W.), Department of Radiology (C.E.L.), and Department of Pathology (J.W.), the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; Image Sciences Institute, University Medical Center Utrecht, Utrecht, the Netherlands (B.H.M.v.d.V., M.A.V., K.G.A.G.); and Faculty of Electrical Engineering, Mathematics, and Computer Science, Delft University of Technology, Delft, the Netherlands (L.F.A.W.)., Canisius S; From the Division of Molecular Carcinogenesis, Oncode Institute (T.B., S.C., L.F.A.W.), Division of Molecular Pathology (S.C., E.H.L., J.W.), Department of Radiology (C.E.L.), and Department of Pathology (J.W.), the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; Image Sciences Institute, University Medical Center Utrecht, Utrecht, the Netherlands (B.H.M.v.d.V., M.A.V., K.G.A.G.); and Faculty of Electrical Engineering, Mathematics, and Computer Science, Delft University of Technology, Delft, the Netherlands (L.F.A.W.)., Lips EH; From the Division of Molecular Carcinogenesis, Oncode Institute (T.B., S.C., L.F.A.W.), Division of Molecular Pathology (S.C., E.H.L., J.W.), Department of Radiology (C.E.L.), and Department of Pathology (J.W.), the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; Image Sciences Institute, University Medical Center Utrecht, Utrecht, the Netherlands (B.H.M.v.d.V., M.A.V., K.G.A.G.); and Faculty of Electrical Engineering, Mathematics, and Computer Science, Delft University of Technology, Delft, the Netherlands (L.F.A.W.)., Loo CE; From the Division of Molecular Carcinogenesis, Oncode Institute (T.B., S.C., L.F.A.W.), Division of Molecular Pathology (S.C., E.H.L., J.W.), Department of Radiology (C.E.L.), and Department of Pathology (J.W.), the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; Image Sciences Institute, University Medical Center Utrecht, Utrecht, the Netherlands (B.H.M.v.d.V., M.A.V., K.G.A.G.); and Faculty of Electrical Engineering, Mathematics, and Computer Science, Delft University of Technology, Delft, the Netherlands (L.F.A.W.)., Viergever MA; From the Division of Molecular Carcinogenesis, Oncode Institute (T.B., S.C., L.F.A.W.), Division of Molecular Pathology (S.C., E.H.L., J.W.), Department of Radiology (C.E.L.), and Department of Pathology (J.W.), the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; Image Sciences Institute, University Medical Center Utrecht, Utrecht, the Netherlands (B.H.M.v.d.V., M.A.V., K.G.A.G.); and Faculty of Electrical Engineering, Mathematics, and Computer Science, Delft University of Technology, Delft, the Netherlands (L.F.A.W.)., Wesseling J; From the Division of Molecular Carcinogenesis, Oncode Institute (T.B., S.C., L.F.A.W.), Division of Molecular Pathology (S.C., E.H.L., J.W.), Department of Radiology (C.E.L.), and Department of Pathology (J.W.), the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; Image Sciences Institute, University Medical Center Utrecht, Utrecht, the Netherlands (B.H.M.v.d.V., M.A.V., K.G.A.G.); and Faculty of Electrical Engineering, Mathematics, and Computer Science, Delft University of Technology, Delft, the Netherlands (L.F.A.W.)., Gilhuijs KGA; From the Division of Molecular Carcinogenesis, Oncode Institute (T.B., S.C., L.F.A.W.), Division of Molecular Pathology (S.C., E.H.L., J.W.), Department of Radiology (C.E.L.), and Department of Pathology (J.W.), the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; Image Sciences Institute, University Medical Center Utrecht, Utrecht, the Netherlands (B.H.M.v.d.V., M.A.V., K.G.A.G.); and Faculty of Electrical Engineering, Mathematics, and Computer Science, Delft University of Technology, Delft, the Netherlands (L.F.A.W.)., Wessels LFA; From the Division of Molecular Carcinogenesis, Oncode Institute (T.B., S.C., L.F.A.W.), Division of Molecular Pathology (S.C., E.H.L., J.W.), Department of Radiology (C.E.L.), and Department of Pathology (J.W.), the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; Image Sciences Institute, University Medical Center Utrecht, Utrecht, the Netherlands (B.H.M.v.d.V., M.A.V., K.G.A.G.); and Faculty of Electrical Engineering, Mathematics, and Computer Science, Delft University of Technology, Delft, the Netherlands (L.F.A.W.).
Jazyk: angličtina
Zdroj: Radiology [Radiology] 2020 Aug; Vol. 296 (2), pp. 277-287. Date of Electronic Publication: 2020 May 26.
DOI: 10.1148/radiol.2020191453
Abstrakt: Background Better understanding of the molecular biology associated with MRI phenotypes may aid in the diagnosis and treatment of breast cancer. Purpose To discover the associations between MRI phenotypes of breast cancer and their underlying molecular biology derived from gene expression data. Materials and Methods This is a secondary analysis of the Multimodality Analysis and Radiologic Guidance in Breast-Conserving Therapy, or MARGINS, study. MARGINS included patients eligible for breast-conserving therapy between November 2000 and December 2008 for preoperative breast MRI. Tumor RNA was collected for sequencing from surgical specimen. Twenty-one computer-generated MRI features of tumors were condensed into seven MRI factors related to tumor size, shape, initial enhancement, late enhancement, smoothness of enhancement, sharpness, and sharpness variation. These factors were associated with gene expression levels from RNA sequencing by using gene set enrichment analysis. Statistical significance of these associations was evaluated by using a sample permutation test and the false discovery rate. Results Gene expression and MRI data were obtained for 295 patients (mean age, 56 years ± 10.3 [standard deviation]). Larger and more irregular tumors showed increased expression of cell cycle and DNA damage checkpoint genes (false discovery rate <0.25; normalized enrichment statistic [NES], 2.15). Enhancement and sharpness of the tumor margin were associated with expression of ribosomal proteins (false discovery rate <0.25; NES, 1.95). Smoothness of enhancement, tumor size, and tumor shape were associated with expression of genes involved in the extracellular matrix (false discovery rate <0.25; NES, 2.25). Conclusion Breast cancer MRI phenotypes were related to their underlying molecular biology revealed by using RNA sequencing. The association between enhancements and sharpness of the tumor margin with the ribosome suggests that these MRI features may be imaging biomarkers for drugs targeting the ribosome. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Cho in this issue.
Databáze: MEDLINE
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