Dataset Information

Heterogeneous Enhancement Patterns of Tumor-adjacent Parenchyma at MR Imaging Are Associated with Dysregulated Signaling Pathways and Poor Survival in Breast Cancer.

ABSTRACT: Purpose To identify the molecular basis of quantitative imaging characteristics of tumor-adjacent parenchyma at dynamic contrast material-enhanced magnetic resonance (MR) imaging and to evaluate their prognostic value in breast cancer. Materials and Methods In this institutional review board-approved, HIPAA-compliant study, 10 quantitative imaging features depicting tumor-adjacent parenchymal enhancement patterns were extracted and screened for prognostic features in a discovery cohort of 60 patients. By using data from The Cancer Genome Atlas (TCGA), a radiogenomic map for the tumor-adjacent parenchymal tissue was created and molecular pathways associated with prognostic parenchymal imaging features were identified. Furthermore, a multigene signature of the parenchymal imaging feature was built in a training cohort (n = 126), and its prognostic relevance was evaluated in two independent cohorts (n = 879 and 159). Results One image feature measuring heterogeneity (ie, information measure of correlation) was significantly associated with prognosis (false-discovery rate < 0.1), and at a cutoff of 0.57 stratified patients into two groups with different recurrence-free survival rates (log-rank P = .024). The tumor necrosis factor signaling pathway was identified as the top enriched pathway (hypergeometric P < .0001) among genes associated with the image feature. A 73-gene signature based on the tumor profiles in TCGA achieved good association with the tumor-adjacent parenchymal image feature (R² = 0.873), which stratified patients into groups regarding recurrence-free survival (log-rank P = .029) and overall survival (log-rank P = .042) in an independent TCGA cohort. The prognostic value was confirmed in another independent cohort (Gene Expression Omnibus GSE 1456), with log-rank P = .00058 for recurrence-free survival and log-rank P = .0026 for overall survival. Conclusion Heterogeneous enhancement patterns of tumor-adjacent parenchyma at MR imaging are associated with the tumor necrosis signaling pathway and poor survival in breast cancer. ^© RSNA, 2017 Online supplemental material is available for this article.

SUBMITTER: Wu J

PROVIDER: S-EPMC5673053 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Heterogeneous Enhancement Patterns of Tumor-adjacent Parenchyma at MR Imaging Are Associated with Dysregulated Signaling Pathways and Poor Survival in Breast Cancer.

Wu Jia J Li Bailiang B Sun Xiaoli X Cao Guohong G Rubin Daniel L DL Napel Sandy S Ikeda Debra M DM Kurian Allison W AW Li Ruijiang R

Radiology 20170714 2

Purpose To identify the molecular basis of quantitative imaging characteristics of tumor-adjacent parenchyma at dynamic contrast material-enhanced magnetic resonance (MR) imaging and to evaluate their prognostic value in breast cancer. Materials and Methods In this institutional review board-approved, HIPAA-compliant study, 10 quantitative imaging features depicting tumor-adjacent parenchymal enhancement patterns were extracted and screened for prognostic features in a discovery cohort of 60 pat ...[more]

PMID: 28708462

Similar Datasets

Project description:Pathway enrichment analysis is a useful tool to study biology and biomedicine, due to its functional screening on well-defined biological procedures rather than separate molecules. The measurement of malfunctions of pathways with a phenotype change, e.g., from normal to diseased, is the key issue when applying enrichment analysis on a pathway. The differentially expressed genes (DEGs) are widely focused in conventional analysis, which is based on the great purity of samples. However, the disease samples are usually heterogeneous, so that, the genes with great differential expression variance (DEVGs) are becoming attractive and important to indicate the specific state of a biological system. In the context of differential expression variance, it is still a challenge to measure the enrichment or status of a pathway. To address this issue, we proposed Integrative Enrichment Analysis (IEA) based on a novel enrichment measurement.The main competitive ability of IEA is to identify dysregulated pathways containing DEGs and DEVGs simultaneously, which are usually under-scored by other methods. Next, IEA provides two additional assistant approaches to investigate such dysregulated pathways. One is to infer the association among identified dysregulated pathways and expected target pathways by estimating pathway crosstalks. The other one is to recognize subtype-factors as dysregulated pathways associated to particular clinical indices according to the DEVGs' relative expressions rather than conventional raw expressions. Based on a previously established evaluation scheme, we found that, in particular cohorts (i.e., a group of real gene expression datasets from human patients), a few target disease pathways can be significantly high-ranked by IEA, which is more effective than other state-of-the-art methods. Furthermore, we present a proof-of-concept study on Diabetes to indicate: IEA rather than conventional ORA or GSEA can capture the under-estimated dysregulated pathways full of DEVGs and DEGs; these newly identified pathways could be significantly linked to prior-known disease pathways by estimated crosstalks; and many candidate subtype-factors recognized by IEA also have significant relation with the risk of subtypes of genotype-phenotype associations.Totally, IEA supplies a new tool to carry on enrichment analysis in the complicate context of clinical application (i.e., heterogeneity of disease), as a necessary complementary and cooperative approach to conventional ones.

Project description:BackgroundThe aim is to assess the time-density curves (TDCs) and correlate the histologic results for small (≤ 2 cm) PDA and surrounding parenchyma at triphasic Multidetector-row CT (MDCT).MethodsTriphasic MDCT scans of 38 consecutive patients who underwent surgery for a small PDA were retrospectively reviewed. The TDCs were analyzed and compared with histologic examination of the PDA and pancreas upstream/downstream in all cases. Three enhancement patterns were identified: 1) enhancement peak during pancreatic parenchymal phase (PPP) followed by a rapid decline on portal venous phase (PVP) and delayed phase (DP) at 5 minutes (type 1 pattern: normal pancreas); 2) maximum enhancement in PVP that gradually decreases in DP (type 2 pattern: mild chronic pancreatitis or PDA with mild fibrous stroma); 3) progressive enhancement with maximum peak in DP (type 3 pattern: severe chronic pancreatitis or PDA with severe fibrous stroma). A p value less than 0.05 was considered statistically significant. Sensitivity was calculated for PDA detection and an attenuation difference with the surrounding tissue of at least 10 HU was considered.ResultsPDA showed type 2 pattern in 5/38 cases (13.2%) and type 3 pattern in 33/38 cases (86,8%). Pancreas upstream to the tumor had type 2 pattern in 20/38 cases (52,6%) and type 3 pattern in 18/38 cases (47,4%). Pancreas downstream to the tumor had type 1 pattern in 19/25 cases (76%) and type 2 pattern in 6/25 cases (24%). Attenuation difference between tumor and parenchyma upstream was higher of 10 UH on PPP in 31/38 patients (sensitivity = 81.6%), on PVP in 29/38 (sensitivity = 76.3%) and on DP in 17/38 (sensitivity = 44.7%). Attenuation difference between tumor and parenchyma downstream was higher of 10 UH on PPP in 25/25 patients (sensitivity = 100%), on PVP in 22/25 (sensitivity = 88%) and on DP in 20/25 (sensitivity = 80%). Small PDAs were isodense to the pancreas upstream to the tumor, and therefore unrecognizable, in 8 cases (8/38; 21%) at qualitative analysis and in 4 cases (4/38; 10,5%) at quantitative analysis.ConclusionsThe quantitative analysis increases the sensitivity for detection of small PDA at triphasic MDCT.

Project description:ObjectivesBecause the distribution volume and mechanism of extracellular and intravascular MR contrast media differ considerably, the enhancement pattern of chronic myocardial infarction with extracellular or intravascular media might also be different. This study aims to investigate the differences in MR enhancement patterns of chronic myocardial infarction between extracellular and intravascular contrast media.Materials and methodsTwenty pigs with myocardial infarction underwent cine MRI, first pass perfusion MRI and delayed enhancement MRI with extracellular or intravascular media at four weeks after coronary occlusion. Myocardial blood flow (MBF) was determined with microsphere measurement. The infarction histopathological changes were evaluated by hematoxylin and eosin staining and Masson's trichrome method.ResultsCine MRI revealed the reduced wall thickening in chronic infarction compared with normal myocardium. Moreover, significant wall thinning in chronic infarction was observed in cine MRI. Peak first-pass signal intensity didn't significantly differ between chronic infarction and normal myocardium no matter what kinds of contrast media. At the following delayed enhancement phase, extracellular media-enhanced signal intensity was significantly higher in chronic infarction than in normal myocardium. Conversely, intravascular media-enhanced signal intensity was almost equivalent among chronic infarction and normal myocardium. At four weeks after infarction, MBF in chronic infarction approached to that in normal myocardium. Large thick-walled vessels were detected at peri-infarction zones. The cardiomyocytes were replaced by scar tissue consisting of dilated blood vessels and discrete fibers of collagen.ConclusionsChronic infarction was characterized by the significantly reduced wall thickening and the definite wall thinning. First-pass myocardial perfusion defect was not detected in chronic infarction with two media due to the significantly recovered MBF and well-developed collateral vessels. Infarction remodeling enlarged the extracellular compartment, which was available for extracellular media but not accessible to intravascular media. Extracellular media identified chronic infarction as the hyper-enhancement; nonetheless, intravascular media didn't provide delayed enhancement.

Dataset Information

Heterogeneous Enhancement Patterns of Tumor-adjacent Parenchyma at MR Imaging Are Associated with Dysregulated Signaling Pathways and Poor Survival in Breast Cancer.

Publications

Heterogeneous Enhancement Patterns of Tumor-adjacent Parenchyma at MR Imaging Are Associated with Dysregulated Signaling Pathways and Poor Survival in Breast Cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets