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Identification of tumor microenvironment-related prognostic genes in colorectal cancer based on bioinformatic methods.

Yi Liu | Long Cheng | Chao Li | Chen Zhang | Lei Wang | Jiantao Zhang
Scientific reports | 2021

Colorectal cancer (CRC) ranks fourth among the deadliest cancers globally, and the progression is highly affected by the tumor microenvironment (TME). This study explores the relationship between TME and colorectal cancer prognosis and identifies prognostic genes related to the CRC microenvironment. We collected the gene expression data from The Cancer Genome Atlas (TCGA) and calculated the scores of stromal/immune cells and their relations to clinical outcomes in colorectal cancer by the ESTIMATE algorithm. Lower immune scores were significantly related to the malignant progression of CRC (metastasis, p = 0.001). We screened 292 differentially expressed genes (DEGs) by dividing CRC cases into high and low stromal/immune score groups. Functional enrichment analyses and protein-protein interaction (PPI) networks illustrated that these DEGs were closely involved in immune response, cytokine-cytokine receptor interaction, and chemokine signaling pathway. Six DEGs (FABP4, MEOX2, MMP12, ERMN, TNFAIP6, and CHST11) with prognostic value were identified by survival analysis and validated in two independent cohorts (GSE17538 and GSE161158). The six DEGs were significantly related to immune cell infiltration levels based on the Tumor Immune Estimation Resource (TIMER). The results might contribute to discovering new diagnostic and prognostic biomarkers and new treatment targets for colorectal cancer.

Pubmed ID: 34294834

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


R Project for Statistical Computing (tool)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

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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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NCBI Epigenomics (tool)

RRID:SCR_006151

THIS RESOURCE IS NO LONGER IN SERVICE, documented on January 19, 2022.

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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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Genomic Data Commons Data Portal (GDC Data Portal) (tool)

RRID:SCR_014514

A unified data repository of the National Cancer Institute (NCI)'s Genomic Data Commons (GDC) that enables data sharing across cancer genomic studies in support of precision medicine. The GDC supports several cancer genome programs at the NCI Center for Cancer Genomics (CCG), including The Cancer Genome Atlas (TCGA), Therapeutically Applicable Research to Generate Effective Treatments (TARGET), and the Cancer Genome Characterization Initiative (CGCI). The GDC Data Portal provides a platform for efficiently querying and downloading high quality and complete data. The GDC also provides a GDC Data Transfer Tool and a GDC API for programmatic access.

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TIMER (tool)

RRID:SCR_018737

Web server for comprehensive analysis of tumor infiltrating immune cells. Web tool for systematical analysis of immune infiltrates across diverse cancer types. Allows users to input function specific parameters, with resulting figures dynamically displayed to access tumor immunological, clinical, and genomic features.

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VennDiagram (tool)

RRID:SCR_002414

Software providing a set of functions to generate high-resolution Venn and Euler plots. Includes handling for several special cases, including two-case scaling, and extensive customization of plot shape and structure.

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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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LIMMA (tool)

RRID:SCR_010943

Software package for the analysis of gene expression microarray data, especially the use of linear models for analyzing designed experiments and the assessment of differential expression.

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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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ggplot2 (tool)

RRID:SCR_014601

Open source software package for statistical programming language R to create plots based on grammar of graphics. Used for data visualization to break up graphs into semantic components such as scales and layers.

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