Screening the key genes of hepatocellular adenoma via microarray analysis of DNA expression and methylation profiles.

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The microarray dataset GSE7473, containing HNF1α-mutated HCA and their corresponding non-tumor livers, 5 HNF1α-mutated HCA and 4 non-related non-tumor livers, was downloaded from the Gene Expression Omnibus (GEO) database. The DNA methylation profile GSE43091, consisting of 50 HCA and 4 normal liver tissues, was also downloaded from the GEO database. Differentially expressed genes (DEGs) were identified by the limma package of R. A t-test was conducted on the differentially methylated sites. Functional enrichment analysis of DEGs was performed through the Database for Annotation, Visualization and Integrated Analysis. The genes corresponding to the differentially methylated sites were obtained by the annotation files of methylation chip platform. A total of 182 DEGs and 3,902 differentially methylated sites were identified in HCA. In addition, 238 enriched GO terms, including organic acid metabolic process and carboxylic acid metabolic process, and 14 KEGG pathways, including chemical carcinogenesis, were identified. Furthermore, 12 DEGs were identified to contain differentially methylated sites, among which, 8 overlapped genes, including pregnancy zone protein and solute carrier family 22 member 1 (SLC22A1), exhibited inverse associations between gene expression levels and DNA methylation levels. The DNA methylation levels may be potential targets of HCA. The present study revealed that the 8 overlapped genes, including annexin A2, chitinase 3-like 1, fibroblast growth factor receptor 4, mal, T-cell differentiation protein like, palladin, cytoskeletal associated protein, plasmalemma vesicle associated protein and SLC22A1, may be potential therapeutic targets of HCA.", "claims": [{"id": "claim-method", "statement": "DEGs were identified using the limma package of R with P<0.05 and |log2 (fold-change)|>1.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:28943905", "locator": "sections[6] \"Identification of differentially methylated sites and differentially expressed genes (DEGs)\" paragraph 2", "quote": "DEGs were identified using the limma package of R with P<0.05 and |log2 (fold-change)|>1."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The gene expression profile (GSE7473) contained 41 samples, including 8 HNF1α-mutated HCA and the corresponding non-tumor liver samples (each sample was assessed four times using 11K_VJF-ARRAY; GPL3282), and 5 HNF1α-mutated HCA and 4 non-related non-tumor liver samples (the 9 samples were assessed using GPL96 Affymetrix Human Genome U133A Array).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:28943905", "locator": "sections[4] \"Microarray data\" paragraph 2", "quote": "The gene expression profile (GSE7473) contained 41 samples, including 8 HNF1α-mutated HCA and the corresponding non-tumor liver samples (each sample was assessed four times using 11K_VJF-ARRAY; GPL3282), and 5 HNF1α-mutated HCA and 4 non-related non-tumor liver samples (the 9 samples were assessed using GPL96 Affymetrix Human Genome U133A Array)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study used the limma package of R to identify DEGs and a t-test to identify differentially methylated sites using GEO datasets GSE7473 and GSE43091; the headline result was 182 DEGs, 3,902 differentially methylated sites, and eight genes showing inverse associations between gene expression and DNA methylation.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:28943905", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The microarray dataset GSE7473, containing HNF1α-mutated HCA and their corresponding non-tumor livers, 5 HNF1α-mutated HCA and 4 non-related non-tumor livers, was downloaded from the Gene Expression Omnibus (GEO) database."}, {"asset": "source:pmid:28943905", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The DNA methylation profile GSE43091, consisting of 50 HCA and 4 normal liver tissues, was also downloaded from the GEO database."}, {"asset": "source:pmid:28943905", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Differentially expressed genes (DEGs) were identified by the limma package of R."}, {"asset": "source:pmid:28943905", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "A t-test was conducted on the differentially methylated sites."}, {"asset": "source:pmid:28943905", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "A total of 182 DEGs and 3,902 differentially methylated sites were identified in HCA."}, {"asset": "source:pmid:28943905", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Furthermore, 12 DEGs were identified to contain differentially methylated sites, among which, 8 overlapped genes, including pregnancy zone protein and solute carrier family 22 member 1 (SLC22A1), exhibited inverse associations between gene expression levels and DNA methylation levels."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study used the limma package of R to identify DEGs and a t-test to identify differentially methylated sites using GEO datasets GSE7473 and GSE43091; the headline result was 182 DEGs, 3,902 differentially methylated sites, and eight genes showing inverse associations between gene expression and DNA methylation.", "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:28943905"], "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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