High-dimensional regression analysis links magnetic resonance imaging features and protein expression and signaling pathway alterations in breast invasive carcinoma

Abstract

BackgroundImaging features derived from MRI scans can be used for not only breast cancer detection and measuring disease extent, but can also determine gene expression and patient outcomes. The relationships between imaging features, gene/protein expression, and response to therapy hold potential to guide personalized medicine. We aim to characterize the relationship between radiologist-annotated tumor phenotypic features (based on MRI) and the underlying biological processes (based on proteomic profiling) in the tumor.MethodsMultiple-response regression of the image-derived, radiologist-scored features with reverse-phase protein array expression levels generated association coefficients for each combination of image-feature and protein in the RPPA dataset. Significantly-associated proteins for features were analyzed with Ingenuity Pathway Analysis software. Hierarchical clustering of the results of the pathway analysis determined which features were most strongly correlated with pathway activity and cellular functions.ResultsEach of the twenty-nine imaging features was found to have a set of significantly correlated molecules, associated biological functions, and pathways.ConclusionsWe interrogated the pathway alterations represented by the protein expression associated with each imaging feature. Our study demonstrates the relationships between biological processes (via proteomic measurements) and MRI features within breast tumors.

Machine learning in breast MRI

“…Radiogenomics also shows promise in the discovery of new genetic signatures . In these studies, correlations between radiomic and genomic profiles are explored in an unsupervised way.…”

“…In these studies, correlations between radiomic and genomic profiles are explored in an unsupervised way. These can lead to new associations; for example, that a certain MR feature (enhancing rim fraction score) is associated with expression of a long noncoding RNA that is known to be associated breast cancer progression and metastasis . This reveals a possible link between a molecular pathway and its manifestation at a macroscopic imaging level.…”