Regulatory Network Analysis to Reveal Important miRNAs and Genes in Non-Small Cell Lung Cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:31376328", "kind": "science-record", "revision": 6, "content_hash": "sha256:3ddbcd6a35174263e449d20a01367e0238c1d4f8ac80e56d81e837dd6462dd84", "created_at": "2026-11-01T15:40:48Z", "updated_at": "2026-11-01T22:00:45Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Regulatory Network Analysis to Reveal Important miRNAs and Genes in Non-Small Cell Lung Cancer.", "doi": "10.22074/cellj.2020.6281", "pmid": "31376328", "authors": ["Xingni Zhou", "Zhenghua Zhang", "Xiaohua Liang"], "journal": "Cell journal", "year": 2020, "abstract": "OBJECTIVE: Lung cancer has high incidence and mortality rate, and non-small cell lung cancer (NSCLC) takes up approximately 85% of lung cancer cases. This study is aimed to reveal miRNAs and genes involved in the mechanisms of NSCLC.\nMATERIALS AND METHODS: In this retrospective study, GSE21933 (21 NSCLC samples and 21 normal samples), GSE27262 (25 NSCLC samples and 25 normal samples), GSE43458 (40 NSCLC samples and 30 normal samples) and GSE74706 (18 NSCLC samples and 18 normal samples) were searched from gene expression omnibus (GEO) database. The differentially expressed genes (DEGs) were screened from the four microarray datasets using MetaDE package, and then conducted with functional annotation using DAVID tool. Afterwards, protein-protein interaction (PPI) network and module analyses were carried out using Cytoscape software. Based on miR2Disease and Mirwalk2 databases, microRNAs (miRNAs)-DEG pairs were selected. Finally, Cytoscape software was applied to construct miRNA-DEG regulatory network.\nRESULTS: Totally, 727 DEGs (382 up-regulated and 345 down-regulated) had the same expression trends in all of the four microarray datasets. In the PPI network, TP53 and FOS could interact with each other and they were among the top 10 nodes. Besides, five network modules were found. After construction of the miRNA-gene network, top 10 miRNAs (such as hsa-miR-16-5p, hsa-let-7b-5p, hsa-miR-15a-5p, hsa-miR-15b-5p, hsa-let-7a-5p and hsa-miR-34a- 5p) and genes (such as HMGA1, BTG2, SOD2 and TP53) were selected.\nCONCLUSION: These miRNAs and genes might contribute to the pathogenesis of NSCLC.", "claims": [{"id": "claim-method", "statement": "Using the MetaDE package in R software (https:// cran.r-project.org/web/packages/MetaDE/) (15), DEGs were screened from the four microarray datasets.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31376328", "locator": "sections[5] \"Meta-analysis\" paragraph 2", "quote": "Using the MetaDE package in R software (https:// cran.r-project.org/web/packages/MetaDE/) (15), DEGs were screened from the four microarray datasets."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Finally, the raw data and platform annotation files under GSE21933 (21 NSCLC and 21 normal samples; platform: GPL6254 Phalanx Human OneArray), GSE27262 (25 NSCLC and 25 normal samples; platform: GPL570 [HG-U133_ Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array), GSE43458 (40 NSCLC and 30 normal samples; platform: GPL6244 [HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array) and GSE74706 (18 NSCLC and 18 normal samples; platform: GPL13497 Agilent-026652 Whole Human Genome Microarray 4x44K v2) were extracted.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31376328", "locator": "sections[3] \"Expression profile data\" paragraph 2", "quote": "Finally, the raw data and platform annotation files under GSE21933 (21 NSCLC and 21 normal samples; platform: GPL6254 Phalanx Human OneArray), GSE27262 (25 NSCLC and 25 normal samples; platform: GPL570 [HG-U133_ Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array), GSE43458 (40 NSCLC and 30 normal samples; platform: GPL6244 [HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array) and GSE74706 (18 NSCLC and 18 normal samples; platform: GPL13497 Agilent-026652 Whole Human Genome Microarray 4x44K v2) were extracted."}], "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:31376328"], "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:GSE21933"], "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:GSE21933"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:31376328", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.22074/cellj.2020.6281", "sha256": "sha256:2dd7a2615c97e3a29eaad80dbb42853076d3e3507f67b010b6027cf20cee4930", "bytes": 17524, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.22074/cellj.2020.6281", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC6722447", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE21933", "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=GSE21933", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE21933", "version": null, "note": "Finally, the raw data and platform annotation files under GSE21933 (21 NSCLC and 21 normal samples; platform: GPL6254 Phalanx Human OneArray), GSE27262 (25 NSCLC and 25 normal samples; platform: GPL570 [HG-U133_ Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array), GSE43458 (40 NSCLC and 30 normal samples; platform: GPL6244 [HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array) and GSE74706 (18 NSCLC and 18 normal samples; platform: GPL13497 Agilent-026652 Whole Human Genome Microarray 4x44K v2) were extracted.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Finally, the raw data and platform annotation files under GSE21933 (21 NSCLC and 21 normal samples; platform: GPL6254 Phalanx Human OneArray), GSE27262 (25 NSCLC and 25 normal samples; platform: GPL570 [HG-U133_ Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array), GSE43458 (40 NSCLC and 30 normal samples; platform: GPL6244 [HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array) and GSE74706 (18 NSCLC and 18 normal samples; platform: GPL13497 Agilent-026652 Whole Human Genome Microarray 4x44K v2) were extracted.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM545615", "GSM545616", "GSM545617", "GSM545618", "GSM545619", "GSM545620", "GSM545621", "GSM545622", "GSM545623", "GSM545624", "GSM545625", "GSM545626", "GSM545627", "GSM545628", "GSM545629", "GSM545630", "GSM545631", "GSM545632", "GSM545633", "GSM545634", "GSM545635", "GSM545636", "GSM545637", "GSM545638", "GSM545639", "GSM545640", "GSM545641", "GSM545642", "GSM545643", "GSM545644", "GSM545645", "GSM545646", "GSM545647", "GSM545648", "GSM545649", "GSM545650", "GSM545651", "GSM545652", "GSM545653", "GSM545654", "GSM545655", "GSM545656"], "sample_count": 42, "group_sizes": null, "group_sizes_basis": null, "platform": "6254", "taxon": "Homo sapiens", "title": "Gene expression profiles of tumor and paired normal lung tissues from primary non-small cell lung cancer (NSCLC) patients in Taiwan.", "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:GSE27262", "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=GSE27262", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE27262", "version": null, "note": "Finally, the raw data and platform annotation files under GSE21933 (21 NSCLC and 21 normal samples; platform: GPL6254 Phalanx Human OneArray), GSE27262 (25 NSCLC and 25 normal samples; platform: GPL570 [HG-U133_ Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array), GSE43458 (40 NSCLC and 30 normal samples; platform: GPL6244 [HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array) and GSE74706 (18 NSCLC and 18 normal samples; platform: GPL13497 Agilent-026652 Whole Human Genome Microarray 4x44K v2) were extracted.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Finally, the raw data and platform annotation files under GSE21933 (21 NSCLC and 21 normal samples; platform: GPL6254 Phalanx Human OneArray), GSE27262 (25 NSCLC and 25 normal samples; platform: GPL570 [HG-U133_ Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array), GSE43458 (40 NSCLC and 30 normal samples; platform: GPL6244 [HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array) and GSE74706 (18 NSCLC and 18 normal samples; platform: GPL13497 Agilent-026652 Whole Human Genome Microarray 4x44K v2) were extracted.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM673870", "GSM673871", "GSM673872", "GSM673873", "GSM673874", "GSM673875", "GSM673876", "GSM673877", "GSM673878", "GSM673879", "GSM673880", "GSM673881", "GSM673882", "GSM673883", "GSM673884", "GSM673885", "GSM673886", "GSM673887", "GSM673888", "GSM673889", "GSM673890", "GSM673891", "GSM673892", "GSM673893", 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platform: GPL6244 [HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array) and GSE74706 (18 NSCLC and 18 normal samples; platform: GPL13497 Agilent-026652 Whole Human Genome Microarray 4x44K v2) were extracted.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM1062765", "GSM1062766", "GSM1062767", "GSM1062768", "GSM1062769", "GSM1062770", "GSM1062771", "GSM1062772", "GSM1062773", "GSM1062774", "GSM1062775", "GSM1062776", "GSM1062777", "GSM1062778", "GSM1062779", "GSM1062780", "GSM1062781", "GSM1062782", "GSM1062783", "GSM1062784", "GSM1062785", "GSM1062786", "GSM1062787", "GSM1062788", "GSM1062789", "GSM1062790", "GSM1062791", "GSM1062792", "GSM1062793", "GSM1062794", "GSM1062795", "GSM1062796", "GSM1062797", "GSM1062798", "GSM1062799", "GSM1062800", "GSM1062801", "GSM1062802", "GSM1062803", "GSM1062804", "GSM1062805", "GSM1062806", "GSM1062807", "GSM1062808", "GSM1062809", "GSM1062810", "GSM1062811", "GSM1062812", "GSM1062813", "GSM1062814", "GSM1062815", 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"version": null, "note": "Pathways enriched for the nodes in module a, b, c, d and e", "structure": {"pmcid": "PMC6722447", "section_index": 8, "section_title": "Construction of miRNA-DEG regulatory network", "row_count": 39, "column_count": 6}, "table": {"label": "Table 1", "caption": "Pathways enriched for the nodes in module a, b, c, d and e", "rows": [[""], ["Module", "Pathway ID", "Pathway name", "Count", "P value", "Genes"], [""], ["a", "hsa03040", "Spliceosome", "5", "1.53E-05", "PRPF8, SNRNP200, SNRPA, SNRPD2, SF3B2"], ["hsa03020", "RNA polymerase", "3", "7.33E-04", "POLR2G, POLR2I, POLR2B"], ["hsa00240", "Pyrimidine metabolism", "3", "7.54E-03", "POLR2G, POLR2I, POLR2B"], ["hsa00230", "Purine metabolism", "3", "2.06E-02", "POLR2G, POLR2I, POLR2B"], ["hsa05169", "Epstein-Barr virus infection", "3", "2.38E-02", "POLR2G, POLR2I, POLR2B"], ["hsa05016", "Huntington’s disease", "3", "2.43E-02", "POLR2G, POLR2I, POLR2B"], ["a", "hsa05166", "HTLV-I infection", "7", "4.62E-04", "EGR1, FOS, ETS1, TP53, NFKBIA, TCF3, NFATC1"], ["hsa04660", "T cell receptor signaling pathway", "5", "7.24E-04", "PTPRC, FOS, MAPK3, NFKBIA, NFATC1"], ["hsa05161", "Hepatitis B", "5", "2.57E-03", "FOS, MAPK3, TP53, NFKBIA, NFATC1"], ["hsa04662", "B cell receptor signaling pathway", "4", "2.61E-03", "FOS, MAPK3, NFKBIA, NFATC1"], ["hsa04010", "MAPK signaling pathway", "6", "3.22E-03", "FOS, MAPK3, TP53, DDIT3, NFATC1, DUSP6"], ["hsa05133", "Pertussis", "4", "3.31E-03", "FOS, IRF8, MAPK3, PYCARD"], ["hsa05215", "Prostate cancer", "4", "5.19E-03", "MAPK3, TP53, NFKBIA, MTOR"], ["hsa04668", "TNF signaling pathway", "4", "8.70E-03", "FOS, MAPK3, EDN1, NFKBIA"], ["hsa04151", "PI3K-Akt signaling pathway", "6", "1.15E-02", "MAPK3, COL3A1, COL6A3, TP53, ITGB4, MTOR"], ["hsa04380", "Osteoclast differentiation", "4", "1.54E-02", "FOS, MAPK3, NFKBIA, NFATC1"], ["hsa04621", "NOD-like receptor signaling pathway", "3", "2.06E-02", "MAPK3, PYCARD, NFKBIA"], ["hsa04921", "Oxytocin signaling pathway", "4", "2.53E-02", "FOS, PRKAG1, MAPK3, NFATC1"], ["hsa05210", "Colorectal cancer", "3", "2.58E-02", "FOS, MAPK3, TP53"], ["hsa05230", "Central carbon metabolism in cancer", "3", "2.73E-02", "MAPK3, TP53, MTOR"], ["hsa05214", "Glioma", "3", "2.81E-02", "MAPK3, TP53, MTOR"], ["hsa04920", "Adipocytokine signaling pathway", "3", "3.23E-02", "PRKAG1, NFKBIA, MTOR"], ["hsa05140", "Leishmaniasis", "3", "3.31E-02", "FOS, MAPK3, NFKBIA"], ["hsa05220", "Chronic myeloid leukemia", "3", "3.40E-02", "MAPK3, TP53, NFKBIA"], ["hsa05132", "Salmonella infection", "3", "4.40E-02", "FOS, MAPK3, PYCARD"], ["hsa04024", "cAMP signaling pathway", "4", "4.49E-02", "FOS, MAPK3, NFKBIA, NFATC1"], ["hsa04512", "ECM-receptor interaction", "3", "4.79E-02", "COL3A1, COL6A3, ITGB4"], ["hsa04510", "Focal adhesion", "4", "4.95E-02", "MAPK3, COL3A1, COL6A3, ITGB4"], ["c", "hsa03022", "Basal transcription factors", "3", "1.24E-04", "CCNH, ERCC3, GTF2B"], ["hsa03420", "Nucleotide excision repair", "2", "2.03E-02", "CCNH, 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