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Molecular profiles of tumor contrast enhancement: A radiogenomic analysis in anaplastic gliomas.

Xing Liu | Yiming Li | Zhiyan Sun | Shaowu Li | Kai Wang | Xing Fan | Yuqing Liu | Lei Wang | Yinyan Wang | Tao Jiang
Cancer medicine | 2018

The presence of contrast enhancement (CE) on magnetic resonance (MR) imaging is conventionally regarded as an indicator for tumor malignancy. However, the biological behaviors and molecular mechanism of enhanced tumor are not well illustrated. The aim of this study was to investigate the molecular profiles associated with anaplastic gliomas (AGs) presenting CE on postcontrast T1-weighted MR imaging. In this retrospective database study, RNA sequencing and MR imaging data of 91 AGs from the Cancer Genome Atlas (TCGA) and 64 from the Chinese Glioma Genome Atlas (CGGA) were collected. Gene set enrichment analysis (GSEA), significant analysis of microarray, generalized linear models, and Least absolute shrinkage and selection operator algorithm were used to explore radiogenomic and prognostic signatures of AG patients. GSEA indicated that angiogenesis and epithelial-mesenchymal transition were significantly associated with post-CE. Genes driving immune system response, cell proliferation, and focal adhesions were also significantly enriched. Gene ontology of 237 differential genes indicated consistent results. A 48-gene signature for CE was identified in TCGA and validated in CGGA dataset (area under the curve = 0.9787). Furthermore, seven genes derived from the CE-specific signature could stratify AG patients into two subgroups based on overall survival time according to corresponding risk score. Comprehensive analysis of post-CE and genomic characteristics leads to a better understanding of radiology-pathology correlations. Our gene signature helps interpret the occurrence of radiological traits and predict clinical outcomes. Additionally, we found nine prognostic quantitative radiomic features of CE and investigated the underlying biological processes of them.

Pubmed ID: 30117304

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This is a list of tools and resources that we have found mentioned in this publication.


CRAN (tool)

RRID:SCR_003005

Network of ftp and web servers around world that store identical, up to date, versions of code and documentation for R. Package archive network for R programming language.

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Cytoscape (tool)

RRID:SCR_003032

Software platform for complex network analysis and visualization. Used for visualization of molecular interaction networks and biological pathways and integrating these networks with annotations, gene expression profiles and other state data.

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The Cancer Genome Atlas (tool)

RRID:SCR_003193

Project exploring the spectrum of genomic changes involved in more than 20 types of human cancer that provides a platform for researchers to search, download, and analyze data sets generated. As a pilot project it confirmed that an atlas of changes could be created for specific cancer types. It also showed that a national network of research and technology teams working on distinct but related projects could pool the results of their efforts, create an economy of scale and develop an infrastructure for making the data publicly accessible. Its success committed resources to collect and characterize more than 20 additional tumor types. Components of the TCGA Research Network: * Biospecimen Core Resource (BCR); Tissue samples are carefully cataloged, processed, checked for quality and stored, complete with important medical information about the patient. * Genome Characterization Centers (GCCs); Several technologies will be used to analyze genomic changes involved in cancer. The genomic changes that are identified will be further studied by the Genome Sequencing Centers. * Genome Sequencing Centers (GSCs); High-throughput Genome Sequencing Centers will identify the changes in DNA sequences that are associated with specific types of cancer. * Proteome Characterization Centers (PCCs); The centers, a component of NCI's Clinical Proteomic Tumor Analysis Consortium, will ascertain and analyze the total proteomic content of a subset of TCGA samples. * Data Coordinating Center (DCC); The information that is generated by TCGA will be centrally managed at the DCC and entered into the TCGA Data Portal and Cancer Genomics Hub as it becomes available. Centralization of data facilitates data transfer between the network and the research community, and makes data analysis more efficient. The DCC manages the TCGA Data Portal. * Cancer Genomics Hub (CGHub); Lower level sequence data will be deposited into a secure repository. This database stores cancer genome sequences and alignments. * Genome Data Analysis Centers (GDACs) - Immense amounts of data from array and second-generation sequencing technologies must be integrated across thousands of samples. These centers will provide novel informatics tools to the entire research community to facilitate broader use of TCGA data. TCGA is actively developing a network of collaborators who are able to provide samples that are collected retrospectively (tissues that had already been collected and stored) or prospectively (tissues that will be collected in the future).

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Gene Set Enrichment Analysis (tool)

RRID:SCR_003199

Software package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.

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MRIcro Software (tool)

RRID:SCR_008264

MRIcro allows Windows and Linux computers view medical images. It is a standalone program, but includes tools to complement SPM (software that allows neuroimagers to analyze MRI, fMRI and PET images). MRIcro allows efficient viewing and exporting of brain images. In addition, it allows neuropsychologists to identify regions of interest (ROIs, e.g. lesions). MRIcro can create Analyze format headers for exporting brain images to other platforms. Some features of MRIcro are: - Converts medical images to SPM friendly Analyze format. - View Analyze format images (big or little endian). - Create Analyze format headers (big or little endian). - Create 3D regions of interest (with computed volume & intensity). - Overlap multiple regions of interest. - Rotate images to match SPM template images. - Export images to BMP, JPEG, PNG or TIF format. - Yoked images: linked viewing of multiple images (e.g. view same coordinates of PET and MRI scans). Users familiar with other Windows programs will find that this software is fairly straightforward to use. Resting the mouse cursor over a button will cause a text hint to appear over the button. However, a tutorial with a step by step guide of how to use MRIcro with SPM is available.

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Cancer Imaging Archive (TCIA) (tool)

RRID:SCR_008927

Archive of medical images of cancer accessible for public download. All images are stored in DICOM file format and organized as Collections, typically patients related by common disease (e.g. lung cancer), image modality (MRI, CT, etc) or research focus. Neuroimaging data sets include clinical outcomes, pathology, and genomics in addition to DICOM images. Submitting Data Proposals are welcomed.

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EnrichmentMap (tool)

RRID:SCR_016052

Source code of a Cytoscape plugin for functional enrichment visualization. It organizes gene-sets, such as pathways and Gene Ontology terms, into a network to reveal which mutually overlapping gene-sets cluster together.

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MATLAB (tool)

RRID:SCR_001622

Multi paradigm numerical computing environment and fourth generation programming language developed by MathWorks. Allows matrix manipulations, plotting of functions and data, implementation of algorithms, creation of user interfaces, and interfacing with programs written in other languages, including C, C++, Java, Fortran and Python. Used to explore and visualize ideas and collaborate across disciplines including signal and image processing, communications, control systems, and computational finance.

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DAVID (tool)

RRID:SCR_001881

Bioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.

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