Biomarker identification and trans-regulatory network analyses in esophageal adenocarcinoma and Barrett's esophagus.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30670912", "kind": "science-record", "revision": 8, "content_hash": "sha256:87ffe52bf36cde5dd950929acfee4e2b530c467db0a6f7f8dd5809af340c38f9", "created_at": "2026-11-01T15:40:41Z", "updated_at": "2026-11-01T22:43:45Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Biomarker identification and trans-regulatory network analyses in esophageal adenocarcinoma and Barrett's esophagus.", "doi": "10.3748/wjg.v25.i2.233", "pmid": "30670912", "authors": ["Jing Lv", "Lei Guo", "Ji-Han Wang", "Yu-Zhu Yan", "Jun Zhang", "Yang-Yang Wang", "Yan Yu", "Yun-Fei Huang", "He-Ping Zhao"], "journal": "World journal of gastroenterology", "year": 2019, "abstract": "BACKGROUND: Esophageal adenocarcinoma (EAC) is an aggressive disease with high mortality and an overall 5-year survival rate of less than 20%. Barrett's esophagus (BE) is the only known precursor of EAC, and patients with BE have a persistent and excessive risk of EAC over time. Individuals with BE are up to 30-125 times more likely to develop EAC than the general population. Thus, early detection of EAC and BE could significantly improve the 5-year survival rate of EAC. Due to the limitations of endoscopic surveillance and the lack of clinical risk stratification strategies, molecular biomarkers should be considered and thoroughly investigated.\nAIM: To explore the transcriptome changes in the progression from normal esophagus (NE) to BE and EAC.\nMETHODS: Two datasets from the Gene Expression Omnibus (GEO) in NCBI Database (https://www.ncbi.nlm.nih.gov/geo/) were retrieved and used as a training and a test dataset separately, since NE, BE, and EAC samples were included and the sample sizes were adequate. This study identified differentially expressed genes (DEGs) using the R/Bioconductor project and constructed trans-regulatory networks based on the Transcriptional Regulatory Element Database and Cytoscape software. Enrichment of Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) terms was identified using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) Bioinformatics Resources. The diagnostic potential of certain DEGs was assessed in both datasets.\nRESULTS: In the GSE1420 dataset, the number of up-regulated DEGs was larger than that of down-regulated DEGs when comparing EAC vs NE and BE vs NE. Among these DEGs, five differentially expressed transcription factors (DETFs) displayed the same trend in expression across all the comparison groups. Of these five DETFs, E2F3, FOXA2, and HOXB7 were up-regulated, while PAX9 and TFAP2C were down-regulated. Additionally, the majority of the DEGs in trans-regulatory networks were up-regulated. The intersection of these potential DEGs displayed the same direction of changes in expression when comparing the DEGs in the GSE26886 dataset to the DEGs in trans-regulatory networks above. The receiver operating characteristic curve analysis was performed for both datasets and found that TIMP1 and COL1A1 could discriminate EAC from NE tissue, while REG1A, MMP1, and CA2 could distinguish BE from NE tissue. DAVID annotation indicated that COL1A1 and MMP1 could be potent biomarkers for EAC and BE, respectively, since they participate in the majority of the enriched KEGG and GO terms that are important for inflammation and cancer.\nCONCLUSION: After the construction and analyses of the trans-regulatory networks in EAC and BE, the results indicate that COL1A1 and MMP1 could be potential biomarkers for EAC and BE, respectively.", "claims": [{"id": "claim-method", "statement": "The Limma package was used to identify the DEGs between any two groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30670912", "locator": "sections[5] \"Identification of differentially expressed genes (DEGs)\" paragraph 2", "quote": "The Limma package was used to identify the DEGs between any two groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Datasets analyzed during the current study are available from the Gene Expression Omnibus (GEO) DataSets in the National Center for Biotechnology Information (NBCI) Database (http://www.ncbi.nlm.nih.gov/gds/). All data generated or analysed during this study are included in this article and its supplementary information files.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30670912", "locator": "sections[23] \"Footnotes\" paragraph 2", "quote": "Datasets analyzed during the current study are available from the Gene Expression Omnibus (GEO) DataSets in the National Center for Biotechnology Information (NBCI) Database (http://www.ncbi.nlm.nih.gov/gds/). All data generated or analysed during this study are included in this article and its supplementary information files."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:30670912"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE1420"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE1420"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:30670912", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3748/wjg.v25.i2.233", "sha256": "sha256:795ebca825934cad5d865aacddbb750034f2cc3538431558c64a0889b6b0fce6", "bytes": 38721, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3748/wjg.v25.i2.233", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC6337015", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE1420", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE1420", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE1420", "version": null, "note": "Datasets analyzed during the current study are available from the Gene Expression Omnibus (GEO) DataSets in the National Center for Biotechnology Information (NBCI) Database (http://www.ncbi.nlm.nih.gov/gds/). All data generated or analysed during this study are included in this article and its supplementary information files.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Datasets analyzed during the current study are available from the Gene Expression Omnibus (GEO) DataSets in the National Center for Biotechnology Information (NBCI) Database (http://www.ncbi.nlm.nih.gov/gds/). All data generated or analysed during this study are included in this article and its supplementary information files.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM23385", "GSM23386", "GSM23387", "GSM23388", "GSM23389", "GSM23390", "GSM23391", "GSM23392", "GSM23395", "GSM23396", "GSM23397", "GSM23398", "GSM23399", "GSM23400", "GSM23401", "GSM23402", "GSM23413", "GSM23417", "GSM23419", "GSM23422", "GSM23424", "GSM23425", "GSM23426", "GSM23427"], "sample_count": 24, "group_sizes": null, "group_sizes_basis": null, "platform": "96", "taxon": "Homo sapiens", "title": "Barrett's esophagus, Barrett's-associated adenocarcinomas and normal esophageal epithelium", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE26886", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE26886", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE26886", "version": null, "note": "Datasets analyzed during the current study are available from the Gene Expression Omnibus (GEO) DataSets in the National Center for Biotechnology Information (NBCI) Database (http://www.ncbi.nlm.nih.gov/gds/). All data generated or analysed during this study are included in this article and its supplementary information files.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Datasets analyzed during the current study are available from the Gene Expression Omnibus (GEO) DataSets in the National Center for Biotechnology Information (NBCI) Database (http://www.ncbi.nlm.nih.gov/gds/). All data generated or analysed during this study are included in this article and its supplementary information files.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM661721", "GSM661722", "GSM661723", "GSM661724", "GSM661725", "GSM661726", "GSM661727", "GSM661728", "GSM661729", "GSM661730", "GSM661731", "GSM661732", "GSM661733", "GSM661734", "GSM661735", "GSM661736", "GSM661737", "GSM661738", "GSM661739", "GSM661740", "GSM661741", "GSM661742", "GSM661743", "GSM661744", "GSM661745", "GSM661746", "GSM661747", "GSM661748", "GSM661749", "GSM661750", "GSM661751", "GSM661752", "GSM661753", "GSM661754", "GSM661755", "GSM661756", "GSM661757", "GSM661758", "GSM661759", "GSM661760", "GSM661761", "GSM661762", "GSM661763", "GSM661764", "GSM661765", "GSM661766", "GSM661767", "GSM661768", "GSM661769", "GSM661770", "GSM661771", "GSM661772", "GSM661773", "GSM661774", "GSM661775", "GSM661776", "GSM661777", "GSM661778", "GSM661779", "GSM661780", "GSM661781", 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groups in the GSE1420 dataset", "structure": {"pmcid": "PMC6337015", "section_index": 11, "section_title": "Transcription factors in DEGs", "row_count": 4, "column_count": 3}, "table": {"label": "Table 1", "caption": "Differentially expressed transcription factors in the comparison groups in the GSE1420 dataset", "rows": [["Comparison group", "Up-regulated TFs", "Down-regulated TFs"], ["EAC vs NE", "ATF3, ATF5, CEBPB, E2F31, EGR1, EGR3, EGR4, FOXA21, HOXA10, HOXB71, MYBL2, NFIB, PPARG, RELB, SMAD6, SP3, STAT1", "PAX91, RARG, SMAD2, TFAP2A, TFAP2B, TFAP2C1, FOXE1, HLF, HOXA4, HOXB2"], ["BE vs NE", "ATF3, E2F31, EPAS1, ETS2, FOS, FOSB, FOXA21, HOXB71, NFIB, PPARG, STAT1", "PAX91, TFAP2B, TFAP2C1, HLF, HOXA1, HOXA4"], ["EAC vs BE", "E2F31, EGR4, FOXA21, HOXA10, HOXB71, MYBL2", "PAX91, PPARD, RARG, TFAP2C1, ELK3, ETS2, FOXE1"]], "row_count": 4, "column_count": 3, "numeric_cells": 6, "header_rows": 1, "locator": "section[11]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:30670912:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:290e1670b802d795ec62f7eb358b0b2a837b24aee6af41cf149ffd18026c90c4", "bytes": 1331, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#T2", "version": null, "note": "Differentially expressed genes in the trans-regulatory networks existed in both GSE1420 and GSE26886 datasets", "structure": {"pmcid": "PMC6337015", "section_index": 12, "section_title": "Bioinformatics analyses of DEGs in the trans-regulatory networks", "row_count": 3, "column_count": 3}, "table": {"label": "Table 2", "caption": "Differentially expressed genes in the trans-regulatory networks existed in both GSE1420 and GSE26886 datasets", "rows": [["Comparison group", "Up-regulated DEGs", "Down-regulated DEGs"], ["EAC vs NE", "UCP2, TOP1, TIMP1, TAP1, STAT11, ST6GAL1, SOCS1, SMURF2, SLC19A1, SKIL, SERPINE1, SDC4, RELB1, RARRES3, PTPN6, PSMB9, PRKCA, PPARG1, PLAUR, PLAU, PECAM1, PDGFA, ODC1, NT5E, NR1H3, NQO1, MYBL21, MUC5AC, MTRR, MMP9, MMP7, MET, MAN2B1, LAMB1, ITGB1, ITGAV, IRF3, IRF1, IGFBP3, ICAM1, HSD17B2, HOXB71, HMGA2, HFE, HEXB, HEXA, GUSB, GBP1, GALC, F2R, ENG, EGR11, DSG2, CXCL1, COL5A2, COL1A2, COL1A1, CFTR, CD14, ATP2A3, APOE, ADAM28, A2M", "TOM1, TGM1, TGFA, TFAP2C1, TFAP2A1, TALDO1, SRPX2, SNAI2, SMARCA2, SMAD21, SLC6A4, SLC13A4, SERPINB2, RORA1, RARG1, PRNP, PPL, PIM1, PEX3, PBX1, OAT, MAPT, MAPK1, LMO2, KRT5, KRT4, KRT16, KRT14, IMPA2, HSPB1, HRAS, HOXA41, HMOX1, HLF1, GSTP1, GM2A, GLUD1, FLG, FGFR3, FCER1A, ETF1, DSG3, DSG1, DBI, CYP11A1, CSTA, CRABP2, CEACAM1, CALB2, BCKDHA, ATP12A, ALDH3A2, AKR1C1, AGA, ADIPOR1, ACOX1, ACAA1"], ["BE vs NE", "UCP2, TIMP1, TGFBR2, SOCS3, REG1A, PPARG1, PLAUR, NR1H3, NQO1, MMP1, KRT18, GDF15, GBP1, FOS1, CA2, ANPEP, A2M", "RORA, HOXA11, FCER1A, CYP11A1, BMP7"]], "row_count": 3, "column_count": 3, "numeric_cells": 4, "header_rows": 1, "locator": 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