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Identification of COL1A1 as an invasion‑related gene in malignant astrocytoma.

Shen Sun | Yue Wang | Yue Wu | Yue Gao | Qi Li | Ayanlaja Abiola Abdulrahman | Xin-Feng Liu | Guang-Quan Ji | Jin Gao | Li Li | Fa-Ping Wan | Yun-Qing Li | Dian-Shuai Gao
International journal of oncology | 2018

Malignant astrocytoma (MA) is the most common and severe type of brain tumor. A greater understanding of the underlying mechanisms responsible for the development of MA would be beneficial for the development of targeted molecular therapies. In the present study, the upregulated differentially expressed genes (DEGs) in MA were obtained from the Gene Expression Omnibus database using R/Bioconductor software. DEGs in different World Health Organization classifications were compared using the Venny tool and 15 genes, including collagen type I α1 chain (COL1A1) and laminin subunit γ1 (LAMC1), were revealed to be involved in the malignant progression of MA. In addition, the upregulated DEGs in MA were evaluated using functional annotations of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes with the Database for Annotation, Visualization, and Integrated Discovery tool. The results indicated that invasion‑associated enrichment was observed in 'extracellular matrix' (ECM), 'cell adhesion' and 'phosphoinositide 3‑kinase‑protein kinase B signaling pathway'. Subsequently, the analysis of the protein‑protein interactions was performed using STRING and Cytoscape software, which revealed that the ECM component was the invasion‑associated module and its corresponding genes included COL1A1, LAMC1 and fibronectin 1. Finally, survival Kaplan‑Meier estimate was conducted using cBioportal online, which demonstrated that COL1A1 expression affected the survival of and recurrence in patients with MA. Moreover, the results of in vitro Transwell assay and western blot analysis revealed that the depleted levels of COL1A1 also decreased the expression of several proteins associated with cell invasion, including phosphorylated‑signal transducer and activator of transcription 3, matrix metalloproteinase (MMP)‑2, MMP‑9 and nuclear factor‑κB. On the whole, the present study identified the invasion‑related target genes and the associated potential pathways in MA. The results indicated that COL1A1 may be a candidate biomarker for the prognosis and treatment of MA.

Pubmed ID: 30272346

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


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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SPSS (tool)

RRID:SCR_002865

Software package used for interactive, or batched, statistical analysis in social science, health sciences and marketing. Software platform offers advanced statistical analysis, a library of machine-learning algorithms, text analysis, open-source extensibility, integration with big data and deployment into applications.Versions that were produced by SPSS Inc. before the IBM acquisition (Versions 18 and earlier) would be given origin or publisher of SPSS Inc. in Chicago.

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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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GenomeNet (tool)

RRID:SCR_004165

GenomeNet is a Japanese network of database and computational services for genome research and related research areas in biomedical sciences, operated by the Kyoto University Bioinformatics Center. GenomeNet was established in September 1991 under the Human Genome Program of the then Ministry of Education, Science and Culture (Monbusho). The GenomeNet service has been developed by the Kanehisa Laboratory in Kyoto University as part of the research projects. GenomeNet is operated using the Supercomputer System of the Institute for Chemical Research, Kyoto University. LinkDB is supported by the National Bioscience Database Center of the Japan Science and Technology Agency.

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Cell Signaling Technology (tool)

RRID:SCR_004431

Privately held company that develops and produces antibodies, ELISA kits, ChIP kits, proteomic kits, and other related reagents used to study cell signaling pathways that impact human health.

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STRING (tool)

RRID:SCR_005223

Database of known and predicted protein interactions. The interactions include direct (physical) and indirect (functional) associations and are derived from four sources: Genomic Context, High-throughput experiments, (Conserved) Coexpression, and previous knowledge. STRING quantitatively integrates interaction data from these sources for a large number of organisms, and transfers information between these organisms where applicable. The database currently covers 5''214''234 proteins from 1133 organisms. (2013)

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ClueGO (tool)

RRID:SCR_005748

A Cytoscape plug-in that visualizes the non-redundant biological terms for large clusters of genes in a functionally grouped network. It can be used in combination with GOlorize. The identifiers can be uploaded from a text file or interactively from a network of Cytoscape. The type of identifiers supported can be easily extended by the user. ClueGO performs single cluster analysis and comparison of clusters. From the ontology sources used, the terms are selected by different filter criteria. The related terms which share similar associated genes can be combined to reduce redundancy. The ClueGO network is created with kappa statistics and reflects the relationships between the terms based on the similarity of their associated genes. On the network, the node colour can be switched between functional groups and clusters distribution. ClueGO charts are underlying the specificity and the common aspects of the biological role. The significance of the terms and groups is automatically calculated. ClueGO is easy updatable with the newest files from Gene Ontology and KEGG. Platform: Windows compatible, Mac OS X compatible, Linux compatible, Unix compatible

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HPA (tool)

RRID:SCR_006710

Public database with millions of high-resolution images showing the spatial distribution of proteins in different normal human tissues and cancer types, as well as different human cell lines. The data is released together with application-specific validation performed for each antibody, including immunohistochemisty, Western blot analysis and, for a large fraction, a protein array assay and immunofluorescent based confocal microscopy. The database has been developed in a gene-centric manner with the inclusion of all human genes predicted from genome efforts. Search functionalities allow for complex queries regarding protein expression profiles, protein classes and chromosome location. Antibodies included have been analyzed using a standardized protocol in a single attempt without further efforts to optimize the procedure and therefore it cannot be excluded that certain observed binding properties are due to technical rather than biological reasons and that further optimization could result in a different outcome. Submission of antibodies: The Swedish Human Proteome Atlas (HPA) program, invites submission of antibodies from both academic and commercial sources to be included in the human protein atlas. All antibodies will be validated by the HPA-program by a standard procedure and antibodies that are accepted will be use in the tissue- profiling program to generate high-resolution immunohistochemistry images representing a wide spectrum of normal tissues and cancer types.

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Gene Expression Omnibus (GEO) (tool)

RRID:SCR_007303

Functional genomics data repository supporting MIAME-compliant data submissions. Includes microarray-based experiments measuring the abundance of mRNA, genomic DNA, and protein molecules, as well as non-array-based technologies such as serial analysis of gene expression (SAGE) and mass spectrometry proteomic technology. Array- and sequence-based data are accepted. Collection of curated gene expression DataSets, as well as original Series and Platform records. The database can be searched using keywords, organism, DataSet type and authors. DataSet records contain additional resources including cluster tools and differential expression queries.

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Millipore (tool)

RRID:SCR_008983

An Antibody supplier

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KEGG (tool)

RRID:SCR_012773

Integrated database resource consisting of 16 main databases, broadly categorized into systems information, genomic information, and chemical information. In particular, gene catalogs in completely sequenced genomes are linked to higher-level systemic functions of cell, organism, and ecosystem. Analysis tools are also available. KEGG may be used as reference knowledge base for biological interpretation of large-scale datasets generated by sequencing and other high-throughput experimental technologies.

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affy (tool)

RRID:SCR_012835

Software R package of functions and classes for the analysis of oligonucleotide arrays manufactured by Affymetrix. Used to process probe level data and for exploratory oligonucleotide array analysis.

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CluePedia Cytoscape plugin (tool)

RRID:SCR_015784

Data analysis software and search tool for new markers potentially associated to pathways. CluePedia calculates linear and non-linear statistical dependencies from experimental data and investigates interrelations within each pathway to reveal associations through gene/protein/miRNA enrichments.

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Gene Expression Omnibus (GEO) (tool)

RRID:SCR_005012

Functional genomics data repository supporting MIAME-compliant data submissions. Includes microarray-based experiments measuring the abundance of mRNA, genomic DNA, and protein molecules, as well as non-array-based technologies such as serial analysis of gene expression (SAGE) and mass spectrometry proteomic technology. Array- and sequence-based data are accepted. Collection of curated gene expression DataSets, as well as original Series and Platform records. The database can be searched using keywords, organism, DataSet type and authors. DataSet records contain additional resources including cluster tools and differential expression queries.

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U-87MG ATCC (tool)

RRID:CVCL_0022

Cell line U-87MG ATCC is a Cancer cell line with a species of origin Homo sapiens (Human)

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U-251MG (tool)

RRID:CVCL_0021

Cell line U-251MG is a Cancer cell line with a species of origin Homo sapiens (Human)

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U-251MG (tool)

RRID:CVCL_0021

Cell line U-251MG is a Cancer cell line with a species of origin Homo sapiens (Human)

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