Identification of key genes and pathways for esophageal squamous cell carcinoma by bioinformatics analysis.

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The microarray dataset GSE20347 was downloaded from the Gene Expression Omnibus (GEO) database, and included 17 tissue samples and 13 normal adjacent tissue samples from patients with ESCC. A total of 22,277 DEGs were identified. A heat map for the DEGs was constructed with the Morpheus online tool and the top 200 genes (100 upregulated and 100 downregulated) were selected for further bioinformatics analysis, including analysis of gene ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, protein-protein interaction networks and Spearman's correlation tests. The results of the GO analysis indicated that the upregulated DEGs were most significantly enriched in membrane-bounded vesicles in the cellular component (CC) category, but were not significantly enriched in any GO terms of the categories biological process (BP) or molecular function (MF); furthermore, the downregulated DEGs were most significantly enriched in regulation of DNA metabolic processes, nucleotide binding and chromosomes in the categories BP, MF and CC, respectively. The KEGG analysis indicated that the downregulated DEGs were enriched in the regulation of cell cycle pathways. The top 10 hub proteins in the protein-protein interaction network were cyclin-dependent kinase 4, budding uninhibited by benzimidazoles 1, cyclin B2, heat shock protein 90AA1, aurora kinase A, H2A histone family member Z, replication factor C subunit 4, and minichromosome maintenance complex component 2, -4 and -7. These proteins are mainly involved in regulating tumor progression. The genes in the four top modules were mainly implicated in regulating cell cycle pathways. Secreted Ly-6/uPAR-related protein (SLURP) was the hub gene, and SLURP and its interacting genes were most enriched in the chromosomal part in the CC category, organelle organization in the BP category and protein binding in the MF category, and were involved in pathways including DNA replication, cell cycle and P53 signaling. The expression of SLURP-1 in fifteen patients with esophageal carcinoma was detected using quantitative polymerase chain reaction analysis, and the results indicated that SLURP-1 expression was significantly decreased in the tumor samples relative to that in normal adjacent tissues. These results suggest that several hub proteins and the hub gene SLURP-1 may serve as potential therapeutic targets, and that gene dysfunction may be involved in the tumorigenesis of ESCC.", "claims": [{"id": "claim-method", "statement": "To further determine DEGs that has the most connections to the other top DEG, a Spearman's correlation test was performed in Excel 2007 (Microsoft Corp., Redmond, WA, USA).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30112053", "locator": "sections[8] \"Spearman correlation test of the top 200DEGs in patients with ESCC\" paragraph 2", "quote": "To further determine DEGs that has the most connections to the other top DEG, a Spearman's correlation test was performed in Excel 2007 (Microsoft Corp., Redmond, WA, USA)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The analyzed data sets generated during the study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30112053", "locator": "sections[23] \"Availability of data and materials\" paragraph 2", "quote": "The analyzed data sets generated during the study are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using the GSE20347 microarray dataset downloaded from GEO and screening the top 200 DEGs by signal-to-noise ratio, the study identified SLURP as the hub gene and found that SLURP-1 expression was significantly decreased in ESCC tumor samples relative to normal adjacent tissues.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:30112053", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The microarray dataset GSE20347 was downloaded from the Gene Expression Omnibus (GEO) database, and included 17 tissue samples and 13 normal adjacent tissue samples from patients with ESCC."}, {"asset": "source:pmid:30112053", "locator": "sections[5] \"Identification of DEGs\" paragraph 2", "quote": "The top 200 DEGs (100 upregulated and 100 downregulated genes) were screened by their signal-to-noise ratio (SNR)."}, {"asset": "source:pmid:30112053", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The expression of SLURP-1 in fifteen patients with esophageal carcinoma was detected using quantitative polymerase chain reaction analysis, and the results indicated that SLURP-1 expression was significantly decreased in the tumor samples relative to that in normal adjacent tissues."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Using the GSE20347 microarray dataset downloaded from GEO and screening the top 200 DEGs by signal-to-noise ratio, the study identified SLURP as the hub gene and found that SLURP-1 expression was significantly decreased in ESCC tumor samples relative to normal adjacent tissues.", "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:30112053"], "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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