ABSTRACT: Radiomic subtyping improves disease stratification beyond key molecular, clinical and standard imaging characteristics in patients with glioblastoma.
Project description:Background: To analyze the potential of radiomics for disease stratification beyond key molecular, clinical and standard imaging features in patients with glioblastoma. Methods: Quantitative imaging features (n=1043) were extracted from the multiparametric MRI of 181 patients with newly-diagnosed glioblastoma prior to standard-of-care treatment (allocated to a discovery and validation set, 2:1 ratio). A subset of 386/1043 features were identified as reproducible (in an independent MRI-test-retest cohort) and selected for analysis. A penalized Cox-model with 10-fold cross-validation (Coxnet) was fitted on the discovery set to construct a radiomic signature for predicting progression-free and overall survival (PFS, OS). The incremental value of a radiomic signature beyond molecular (MGMT-promoter methylation, DNA-methylation subgroups), clinical (patients age, KPS, extent-of-resection, adjuvant treatment) and standard imaging parameters (tumor volumes) for stratifying PFS and OS was assessed with multivariate Cox-models (performance quantified with prediction error curves). Results: The radiomic signature (constructed from 8/386 features identified through Coxnet) increased the prediction accuracy for PFS and OS (in both discovery and validation set) beyond the assessed molecular, clinical and standard imaging parameters (p≤0.01). Prediction errors decreased by 36% for PFS and 37% for OS when adding the radiomic signature (as compared to 29% and 27% with molecular + clinical features alone). The radiomic signature was - along with MGMT-status - the only parameter with independent significance on multivariate analysis (p≤0.01). Conclusions: Our study stresses the role of integrating radiomics into a multi-layer decision framework with key molecular and clinical features to improve disease stratification and to potentially advance personalized treatment of patients with glioblastoma.
Project description:To determine whether adding Decipher to standard risk stratification tools (CAPRA-S and Stephenson nomogram) improves accuracy in prediction of metastatic disease within 5 years after surgery in men with adverse pathologic features after RP.
Project description:The key radiomic features were found to vary after neoadjuvant chemotherapy. Moreover, lncRNAs were discovered to be significantly correlated with radiomics and recurrence-free survival (RFS). The findings indicate that the radiomic signature can be conveniently used for individualized prediction of RFS and that radiomics is associated with lncRNAs in breast cancer.
Project description:To determine whether adding Decipher to standard risk stratification tools (CAPRA-S and Stephenson nomogram) improves accuracy in prediction of metastatic disease within 5 years after surgery in men with adverse pathologic features after RP. The study population consisted of 182 patients selected from 2,641 men who underwent RP at the Cleveland Clinic between 1987-2008 who met the following criteria: 1) preoperative PSA>20 ng/mL, stage pT3 or margin positive, or Gleason score >/8; 2) pathologic node negative; 3) undetectable post-RP PSA; 4) no neoadjuvant or adjuvant therapy; and 5) minimum of 5 years follow-up for the controls.
Project description:Introduction: The aim of this pilot study is to establish a radiogenomic characterisation of a clear-cell renal cell carcinoma (ccRCC) subpopulation, focusing on the transcriptomic underpinnings of radiomic features. Materials & Methods: To establish the viability of conducting a combined analysis of both radiomic and genomic data, a pilot cohort of 6 patients with <5cm G2 unilateral non-metastatic T1a-b ccRCC, who underwent surgery, was evaluated. Transcriptomic analysis was conducted through RNA-seq on tumor samples, while radiomic data was extracted from pre-operative 4 phase contrast-enhanced multidetector CT scans. Genomic heterogeneity was assessed with principal component analysis run on unrestricted data, on a clear-cell renal cell carcinoma associated gene list with zero-centered Reads Per Kilobase of transcript, per million mapped reads values. The underlying pathways and gene ontologies were established with enrichment analysis. In addition, Pearson’s correlation between radiomic data and the transcription of significant genes was fitted, and dendrogram and heatmap plots were drawn. Results: Even in a clinically homogeneous population, the employed analyses have demonstrated that RCC should be regarded as an intrinsically heterogeneous disease. The analysis of the radiomic features and gene expression correlation using heatmap and dendrogram showed four distinct radiogenomic correlation patterns: with one including 5 radiomic features, and the other three including 2 features each. Conclusion: The current pilot study is the first investigation demonstrating an innovative radiogenomic characterisation of clear-cell RCC. Based on such observations, further investigation into the radiomic and genomic approaches for the enhanced diagnosis of RCC is warranted.
Project description:We report the application of RNA-seq for molecular profiling of cultured, U87MG cells that stably express TrkB. Our data set is based on about 40 million unique reads per sample, in four independent mRNA preparations, for nine different testing conditions. U87MG is a standard human glioblastoma patient derived cell line. It serves as a cellular model for studying molecular characteristics of glioblastoma. We describe in our study the intracellular self-activation of TrkB via Y705 and its role in reducing actin dynamics and cell migraton. With this transcriptome dataset, we wished to highlight key players that are activated after TrkB self-activation. The dataset suggest a transcriptional level reprogramming and switching on of several genes that play a role in modulating immune responses and defense mechanisms, in the modified U87MG cells.
Project description:Comparison the mRNA expression profiles of 101 CRC tissues to those from matched 35 non-neoplastic colon mucosal tissues from patients with stage III CRCs treated with FOLFOX adjuvant chemotherapy in each molecular subtype. Gene expression–based subtyping is widely accepted as a relevant source of disease stratification. Results provide important information of molecular marker genes for molecular classification.
Project description:Revised risk estimation and treatment stratification of low- and intermediate-risk neuroblastoma patients by integrating clinical and molecular prognostic markers. To optimize neuroblastoma treatment stratification, we aimed at developing a novel risk estimation system by integrating gene expression-based classification and established prognostic markers. Gene expression profiles were generated from 709 neuroblastoma specimens using customized 4x44K microarrays. Classification models were built using 75 tumors with contrasting courses of disease. Validation was performed in an independent test set (n=634) by Kaplan-Meier estimates and Cox regression analyses. Combination of gene expression-based classification and established prognostic markers improves risk estimation of LR/IR neuroblastoma patients. We propose to implement our revised treatment stratification system in a prospective clinical trial.
Project description:Background:To evaluate the association of multiparametric and multiregional MRI-features with key molecular characteristics in patients with newly-diagnosed glioblastoma. Methods:Retrospective data evaluation was approved by the local ethics committee of the University of Heidelberg (ethics approval number: S-320/2012) and informed consent was waived. Preoperative MRI-features were correlated with key molecular characteristics within a single-institutional cohort of 152 patients with newly-diagnosed glioblastoma. Preoperative MRI-features (n=31) included multiparametric (anatomical, diffusion-, perfusion-, and susceptibility-weighted images) and multiregional (contrast enhancing and non-enhancing FLAIR-hyperintense) information with (histogram) quantification of tumor volumes, volume ratios, apparent diffusion coefficients, cerebral blood flow / volume (CBF / CBV) and intratumoral susceptibility signals. Molecular characteristics determined with the Illumina Infinium HumanMethylation450 array included global DNA-methylation subgroups (e.g. mesenchymal (MES), RTK I “PGFRA”, RTK II “classic”), MGMT-promoter methylation status and hallmark copy-number-variations (EGFR-, PDGFRA-, MDM4- and CDK4-amplification; PTEN-, CDKN2A-, NF1- and RB1-loss). Univariate analyses (voxel-lesion-symptom-mapping for tumor location, Wilcoxon-test for all other MRI-features) as well as machine-learning models were applied to study the strength of association and discriminative value of MRI-features for predicting underlying molecular characteristics. Results: There was no tumor location predilection for any of the assessed molecular parameters (permutation-adjusted p>0.05 each). Univariate imaging parameter associations were noted for EGFR amplification and CDKN2A loss, both demonstrating increased nrCBV and nrCBF values (performance of these parameters, as assessed by the area under the ROC curve ranged from 63 to 69%, FDR-adjusted p<0.05, respectively). Subjecting all MRI-features to machine-learning-based classification allowed to predict EGFR amplification status and the RTK II “classic” GB subgroup with a moderate, yet significantly greater accuracy (63% for EGFR [p<0.01] and 61% for RTK II [p=0.01]) than the prediction by chance, whereas prediction accuracy for all other molecular parameters was non-significant (p>0.05, all models). Conclusions: In summary, we found univariate associations between established MRI-features and molecular characteristics, however not of sufficient strength to allow the generation of machine-learning classification models for reliable and clinically meaningful prediction of the assessed molecular characteristics in patients with newly-diagnosed glioblastoma.