Transcriptome profiling identifies genes and pathways deregulated upon floxuridine treatment in colorectal cancer cells harboring GOF mutant p53.

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Certain tumor associated p53 missense mutants acquire gain-of-function (GOF) properties and confer oncogenic phenotypes including enhanced chemoresistance. The colorectal cancers (CRC) harboring mutant p53 are generally aggressive in nature and difficult to treat. To identify a potential gene expression signature of GOF mutant p53-driven acquired chemoresistance in CRC, we performed transcriptome profiling of floxuridine (FUdR) treated SW480 cells expressing mutant p53(R273H) (GEO#: GSE77533). We obtained several genes differentially regulated between FUdR treated and untreated cells. Further, functional characterization and pathway analysis revealed significant enrichment of crucial biological processes and pathways upon FUdR treatment in SW480 cells. Our data suggest that in response to chemotherapeutics treatment, cancer cells with GOF mutant p53 can modulate key cellular pathways to withstand the cytotoxic effect of the drugs. The genes and pathways identified in the present study can be further validated and targeted for better chemotherapy response in colorectal cancer patients harboring mutant p53.", "claims": [{"id": "claim-method", "statement": "Differential expression analysis was carried out in R Bioconductor Limma package and the p-values were corrected for multiple testing using Benjamini and Hochberg false discovery rate (FDR) algorithm [7].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:27114909", "locator": "sections[9] \"Data analysis\" paragraph 2", "quote": "Differential expression analysis was carried out in R Bioconductor Limma package and the p-values were corrected for multiple testing using Benjamini and Hochberg false discovery rate (FDR) algorithm [7]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Deposited data can be found in the Gene Expression Omnibus (GEO) database:\nhttp://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE77533", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:27114909", "locator": "sections[2] \"Direct link to deposited data\" paragraphs 1-3", "quote": "Deposited data can be found in the Gene Expression Omnibus (GEO) database:\nhttp://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE77533"}], "state": "complete"}, {"id": "claim-target-result", "statement": "The paper used differential-expression analysis with Benjamini–Hochberg false discovery rate correction, identifying 208 up-regulated and 155 down-regulated genes by at least 1.5-fold with FDR-adjusted p-value < 0.05 after FUdR treatment; the source data are deposited in GEO under accession GSE77533 and linked at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE77533.", "kind": "quantitative", "target": {"value": 1.5, "unit": "fold change", "tolerance": null, "source": "We found 208 genes were up-regulated and 155 genes were down-regulated by at least 1.5 fold with FDR-adjusted p-value < 0.05 (Fig. 2D) upon FUdR treatment in SW480 cells."}, "evidence": [{"asset": "source:pmid:27114909", "locator": "sections[9] \"Data analysis\" paragraph 2", "quote": "Differential expression analysis was carried out in R Bioconductor Limma package and the p-values were corrected for multiple testing using Benjamini and Hochberg false discovery rate (FDR) algorithm [7]."}, {"asset": "source:pmid:27114909", "locator": "sections[9] \"Data analysis\" paragraph 2", "quote": "We found 208 genes were up-regulated and 155 genes were down-regulated by at least 1.5 fold with FDR-adjusted p-value < 0.05 (Fig. 2D) upon FUdR treatment in SW480 cells."}, {"asset": "source:pmid:27114909", "locator": "sections[2] \"Direct link to deposited data\" paragraph 2", "quote": "Deposited data can be found in the Gene Expression Omnibus (GEO) database:"}, {"asset": "source:pmid:27114909", "locator": "sections[2] \"Direct link to deposited data\" paragraph 3", "quote": "http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE77533"}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The paper used differential-expression analysis with Benjamini–Hochberg false discovery rate correction, identifying 208 up-regulated and 155 down-regulated genes by at least 1.5-fold with FDR-adjusted p-value < 0.05 after FUdR treatment; the source data are deposited in GEO under accession GSE77533 and linked at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE77533.", "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:27114909"], "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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