Integration of proteomics with CT-based qualitative and radiomic features in high-grade serous ovarian cancer patients: an exploratory analysis.

OBJECTIVES: To investigate the association between CT imaging traits and texture metrics with proteomic data in patients with high-grade serous ovarian cancer (HGSOC). METHODS: This retrospective, hypothesis-generating study included 20 patients with HGSOC prior to primary cytoreductive surgery. Two readers independently assessed the contrast-enhanced computed tomography (CT) images and extracted 33 imaging traits, with a third reader adjudicating in the event of a disagreement. In addition, all sites of suspected HGSOC were manually segmented texture features which were computed from each tumor site. Three texture features that represented intra- and inter-site tumor heterogeneity were used for analysis. An integrated analysis of transcriptomic and proteomic data identified proteins with conserved expression between primary tumor sites and metastasis. Correlations between protein abundance and various CT imaging traits and texture features were assessed using the Kendall tau rank correlation coefficient and the Mann-Whitney U test, whereas the area under the receiver operating characteristic curve (AUC) was reported as a metric of the strength and the direction of the association. P values < 0.05 were considered significant. RESULTS: Four proteins were associated with CT-based imaging traits, with the strongest correlation observed between the CRIP2 protein and disease in the mesentery (p < 0.001, AUC = 0.05). The abundance of three proteins was associated with texture features that represented intra-and inter-site tumor heterogeneity, with the strongest negative correlation between the CKB protein and cluster dissimilarity (p = 0.047, τ = 0.326). CONCLUSION: This study provides the first insights into the potential associations between standard-of-care CT imaging traits and texture measures of intra- and inter-site heterogeneity, and the abundance of several proteins. KEY POINTS: • CT-based texture features of intra- and inter-site tumor heterogeneity correlate with the abundance of several proteins in patients with HGSOC. • CT imaging traits correlate with protein abundance in patients with HGSOC.

Radiogenomics of High-Grade Serous Ovarian Cancer: Multireader Multi-Institutional Study from the Cancer Genome Atlas Ovarian Cancer Imaging Research Group.

Purpose To evaluate interradiologist agreement on assessments of computed tomography (CT) imaging features of high-grade serous ovarian cancer (HGSOC), to assess their associations with time-to-disease progression (TTP) and HGSOC transcriptomic profiles (Classification of Ovarian Cancer [CLOVAR]), and to develop an imaging-based risk score system to predict TTP and CLOVAR profiles. Materials and Methods This study was a multireader, multi-institutional, institutional review board-approved, HIPAA-compliant retrospective analysis of 92 patients with HGSOC (median age, 61 years) with abdominopelvic CT before primary cytoreductive surgery available through the Cancer Imaging Archive. Eight radiologists from the Cancer Genome Atlas Ovarian Cancer Imaging Research Group developed and independently recorded the following CT features: characteristics of primary ovarian mass(es), presence of definable mesenteric implants and infiltration, presence of other implants, presence and distribution of peritoneal spread, presence and size of pleural effusions and ascites, lymphadenopathy, and distant metastases. Interobserver agreement for CT features was assessed, as were univariate and multivariate associations with TTP and CLOVAR mesenchymal profile (worst prognosis). Results Interobserver agreement for some features was strong (eg, α = .78 for pleural effusion and ascites) but was lower for others (eg, α = .08 for intraparenchymal splenic metastases). Presence of peritoneal disease in the right upper quadrant (P = .0003), supradiaphragmatic lymphadenopathy (P = .0004), more peritoneal disease sites (P = .0006), and nonvisualization of a discrete ovarian mass (P = .0037) were associated with shorter TTP. More peritoneal disease sites (P = .0025) and presence of pouch of Douglas implants (P = .0045) were associated with CLOVAR mesenchymal profile. Combinations of imaging features contained predictive signal for TTP (concordance index = 0.658; P = .0006) and CLOVAR profile (mean squared deviation = 1.776; P = .0043). Conclusion These results provide some evidence of the clinical and biologic validity of these image features. Interobserver agreement is strong for some features, but could be improved for others. © RSNA, 2017 Online supplemental material is available for this article.

Multiple-response regression analysis links magnetic resonance imaging features to de-regulated protein expression and pathway activity in lower grade glioma.

BACKGROUND AND PURPOSE: Lower grade gliomas (LGGs), lesions of WHO grades II and III, comprise 10-15% of primary brain tumors. In this first-of-a-kind study, we aim to carry out a radioproteomic characterization of LGGs using proteomics data from the TCGA and imaging data from the TCIA cohorts, to obtain an association between tumor MRI characteristics and protein measurements. The availability of linked imaging and molecular data permits the assessment of relationships between tumor genomic/proteomic measurements with phenotypic features. MATERIALS AND METHODS: Multiple-response regression of the image-derived, radiologist scored features with reverse-phase protein array (RPPA) expression levels generated correlation coefficients for each combination of image-feature and protein or phospho-protein in the RPPA dataset. Significantly-associated proteins for VASARI features were analyzed with Ingenuity Pathway Analysis software. Hierarchical clustering of the results of the pathway analysis was used to determine which feature groups were most strongly correlated with pathway activity and cellular functions. RESULTS: The multiple-response regression approach identified multiple proteins associated with each VASARI imaging feature. VASARI features were found to be correlated with expression of IL8, PTEN, PI3K/Akt, Neuregulin, ERK/MAPK, p70S6K and EGF signaling pathways. CONCLUSION: Radioproteomics analysis might enable an insight into the phenotypic consequences of molecular aberrations in LGGs.