Metastatic melanoma: An integrated analysis to identify critical regulators associated with prognosis, pathogenesis and targeted therapies.
Metastatic melanoma causes a high rate of mortality. We conducted an integrated analysis to identify critical regulators associated with the prognosis, pathogenesis, and targeted therapies of metastatic-melanoma. A microarray dataset, GSE15605, including 12 metastatic-melanoma and sixteen normal skin (NS) samples, were obtained from the GEO database. After exploration of DEGs of NS and metastatic-melanoma, identification of relevant transcription factors (TFs) and kinases, the Gene Ontology (GO), and pathways analyses of DEGs were performed. Protein-protein interaction (PPI) networks were evaluated by the STRING and Cytoscape. Subsequently, the hub genes were selected using GEPIA. Survival analysis was performed using the TCGA. To identify microRNA and lncRNA DEGs of the melanoma-associated genes miRwalk and FANTOM6 were employed. In metastatic-melanoma samples 285 and 1173 genes were up and down-regulated, respectively. The upregulated genes were mostly involved in granulocyte chemotaxis, positive regulation of calcium ion transmembrane transport, and melanin biosynthetic process. Five hub genes including CXCL11, ICAM1, LEF1, MITF, and STAT1 were identified, SUZ12, SOX2, TCF3, NANOG, and SMAD4 were determined as the most significant TFs in metastatic-melanoma. Furthermore, CDK2, GSK3B, CSNK2A1, and CDK1 target the highest amounts of genes associated with disease. The DGIdb analysis results show the match drugs for five hub genes. MiRNAs analysis revealed hsa-miR-181c-5p, hsa-miR-30b-3p, hsa-miR-3680-3P, hsa-miR-4659a-3p, hsa-miR-4687-3P, and hsa-miR-6808-3P could regulate the hub genes, whereas RP11-553K8.5 and SRP14-AS1 were identified as the top significant lncRNA. The items recognized in the current study can be used as potential biomarkers for diagnostic, predictive, and might helpful to develop targeted combined therapies.
Pubmed ID: 39820173 RIS Download
Research resources used in this publication
None foundAdditional research tools detected in this publication
- Enrichr (RRID:SCR_001575)
- Cytoscape (RRID:SCR_003032)
- Gene Set Enrichment Analysis (RRID:SCR_003199)
- PubChem (RRID:SCR_004284)
- Entrez GEO Profiles (RRID:SCR_004584)
- STRING (RRID:SCR_005223)
- ChEA (RRID:SCR_005403)
- DGIdb (RRID:SCR_006608)
- HPA (RRID:SCR_006710)
- AutoDock (RRID:SCR_012746)
- KEGG (RRID:SCR_012773)
- UALCAN (RRID:SCR_015827)
- Gene Expression Profiling Interactive Analysis (RRID:SCR_018294)
- PyRx (RRID:SCR_018548)
Antibodies used in this publication
None foundAssociated grants
NonePublication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This is a list of tools and resources that we have found mentioned in this publication.
Enrichr (tool)
RRID:SCR_001575
A web-based gene list enrichment analysis tool that provides various types of visualization summaries of collective functions of gene lists. It includes new gene-set libraries, an alternative approach to rank enriched terms, and various interactive visualization approaches to display enrichment results using the JavaScript library, Data Driven Documents (D3). The software can also be embedded into any tool that performs gene list analysis. System-wide profiling of genes and proteins in mammalian cells produce lists of differentially expressed genes / proteins that need to be further analyzed for their collective functions in order to extract new knowledge. Once unbiased lists of genes or proteins are generated from such experiments, these lists are used as input for computing enrichment with existing lists created from prior knowledge organized into gene-set libraries.
View all literature mentionsCytoscape (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.
View all literature mentionsGene 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.
View all literature mentionsPubChem (tool)
RRID:SCR_004284
Collection of information about chemical structures and biological properties of small molecules and siRNA reagents hosted by the National Center for Biotechnology Information (NCBI).
View all literature mentionsEntrez GEO Profiles (tool)
RRID:SCR_004584
The GEO Profiles database stores gene expression profiles derived from curated GEO DataSets. Each Profile is presented as a chart that displays the expression level of one gene across all Samples within a DataSet. Experimental context is provided in the bars along the bottom of the charts making it possible to see at a glance whether a gene is differentially expressed across different experimental conditions. Profiles have various types of links including internal links that connect genes that exhibit similar behaviour, and external links to relevant records in other NCBI databases. GEO Profiles can be searched using many different attributes including keywords, gene symbols, gene names, GenBank accession numbers, or Profiles flagged as being differentially expressed.
View all literature mentionsSTRING (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)
View all literature mentionsChEA (tool)
RRID:SCR_005403
Data analysis service for gene-list enrichment analysis against a manual database. It allows users to input lists of mammalian gene symbols for which the program computes over-representation of transcription factor targets from the ChIP-X database. The database integrates interaction data from ChIP-chip, ChIP-seq, ChIP-PET and DamID studies and contains 189,933 interactions, manually extracted from 87 publications, describing the binding of 92 transcription factors to 31,932 target genes.
View all literature mentionsDGIdb (tool)
RRID:SCR_006608
A database of drug-gene relationships that provides drug-gene interactions and potential druggability data given list of genes. There are about 15 data sources that are being aggregated by DGIdb, with update date and these data sources are listed on this page: http://dgidb.genome.wustl.edu/sources
View all literature mentionsHPA (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.
View all literature mentionsAutoDock (tool)
RRID:SCR_012746
Software suite of automated docking tools. Designed to predict how small molecules, such as substrates or drug candidates, bind to receptor of known 3D structure. AutoDock consist of AutoDock 4 and AutoDock Vina. AutoDock 4 consists of autodock to perform docking of ligand to set of grids describing target protein, and autogrid to pre calculate these grids.
View all literature mentionsKEGG (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.
View all literature mentionsUALCAN (tool)
RRID:SCR_015827
Web application and database for analyzing cancer transcriptome data. It also has applications is facilitating tumor subgroup gene expression and survival analyses.
View all literature mentionsGene Expression Profiling Interactive Analysis (tool)
RRID:SCR_018294
Web server for cancer and normal gene expression profiling and interactive analyses. Interactive web server for analyzing RNA sequencing expression data of tumors and normal samples from TCGA and GTEx projects, using standard processing pipeline. Provides customizable functions such as tumor or normal differential expression analysis, profiling according to cancer types or pathological stages, patient survival analysis, similar gene detection, correlation analysis and dimensionality reduction analysis.
View all literature mentionsPyRx (tool)
RRID:SCR_018548
Open source virtual screening software for computational drug discovery with intuitive user interface. Runs on operating systems Linux, Windows, and Mac OS. Used to screen libraries of compounds against potential drug targets.
View all literature mentions
