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pmid:35991839
Cancer-Associated Stromal Fibroblast-Derived Transcriptomes Predict Poor Clinical Outcomes and Immunosuppression in Colon Cancer.
Jie Wang · Rehana Akter · Md Fahim Shahriar · Md Nazim Uddin
Pathology oncology research : POR · 2022 doi:10.3389/pore.2022.1610350
Paper
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Experiment
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Data
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Analysis
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Execution
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Complete file
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However, identification of key transcriptomes and their correlations with the survival prognosis, immunosuppression, tumor progression, and metastasis in colon cancer remains lacking. Methods: We used the GSE46824, GSE70468, GSE17536, GSE35602, and the cancer genome atlas (TCGA) colon adenocarcinoma (COAD) datasets for this study. We identified the differentially expressed genes (DEGs), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, hub genes, and survival-associated genes in colon cancer. Finally, we investigated the correlation of key genes with the survival prognosis, immunosuppression, and metastasis. Results: We identified 246 common DEGs between the GSE46824 and GSE70468 datasets of colonic CAFs, which included 72 upregulated and 174 downregulated genes. The upregulated pathways are mainly involved with cancers and cellular signaling, and downregulated pathways are involved with immune regulation and cellular metabolism. The search tool for the retrieval of interacting genes (STRING)-based analysis identified 15 hub genes and 9 significant clusters in colonic CAFs. The upregulation of CTHRC1, PDGFC, PDLIM3, NTM, and SLC16A3 and downregulation of FBN2 are correlated with a shorter survival time in colon cancer. The CTHRC1, PDGFC, PDLIM3, and NTM genes are positively correlated with the infiltration of tumor-associated macrophages (TAM), macrophages, M2 macrophages, the regulatory T cells (Tregs), T cell exhaustion, and myeloid-derived suppressor cells (MDSCs), indicating the immunosuppressive roles of these transcriptomes in colon cancer. Moreover, the CTHRC1, PDGFC, PDLIM3, NTM, and SLC16A3 genes are gradually increased from normal tissue to the tumor and tumor to the metastatic tumor, and FBN2 showed the reverse pattern. Furthermore, the CTHRC1, FBN2, PDGFC, PDLIM3, and NTM genes are positively correlated with the metastatic scores in colon cancer. Then, we revealed that the expression value of CTHRC1, FBN2, PDGFC, PDLIM3, NTM, and SLC16A3 showed the diagnostic efficacy in colonic CAFs. Finally, the expression level of CTHRC1, PDGFC, and NTM genes are consistently altered in colon tumor stroma as well as in the higher CAFs-group of TCGA COAD patients. Conclusion: The identified colonic CAFs-derived key genes are positively correlated with survival prognosis, immunosuppression, tumor progression, and metastasis.", "claims": [{"id": "claim-method", "statement": "GEO2R tool identified the significant DEGs by utilizing the GEOquery [25] and limma R packages [26] from the Bioconductor project (http://www.bioconductor.org/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35991839", "locator": "sections[4] \"Identification of Differentially Expressed Genes\" paragraph 2", "quote": "GEO2R tool identified the significant DEGs by utilizing the GEOquery [25] and limma R packages [26] from the Bioconductor project (http://www.bioconductor.org/)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The GEO datasets GSE46824, GSE70468, GSE17536, and GSE35602 were used in this study and are available in The National Biotechnology Information Centre Gene (NCBI-Gene) database (https://www.ncbi.nlm.nih.gov/gene). 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The TCGA-COAD cohort was downloaded from The Cancer Genome Atlas (TCGA) database (https://portal.gdc.cancer.gov/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The paper used the GEO2R tool with GEOquery and limma to identify differentially expressed genes from two colonic CAF expression datasets, GSE46824 and GSE70468, and then identified their common DEGs.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35991839", "locator": "sections[4] \"Identification of Differentially Expressed Genes\" paragraph 2", "quote": "The differential expression was screened by using GEO2R (http://www.ncbi.nlm.nih.gov/geo/geo2r), which is an interactive web tool to identify the DEGs."}, {"asset": "source:pmid:35991839", "locator": "sections[4] \"Identification of Differentially Expressed Genes\" paragraph 2", "quote": "GEO2R tool identified the significant DEGs by utilizing the GEOquery [25] and limma R packages [26] from the Bioconductor project (http://www.bioconductor.org/)."}, {"asset": "source:pmid:35991839", "locator": "sections[4] \"Identification of Differentially Expressed Genes\" paragraph 2", "quote": "We utilized the online tool “Calculate and draw custom Venn diagrams” (http://bioinformatics.psb.ugent.be/webtools/Venn/) for identifying common DEGs in both datasets."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The paper used the GEO2R tool with GEOquery and limma to identify differentially expressed genes from two colonic CAF expression datasets, GSE46824 and GSE70468, and then identified their common DEGs.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:35991839"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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