Identification and Integrated Analysis of Key Biomarkers for Diagnosis and Prognosis of Non-Small Cell Lung Cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:31805030", "kind": "science-record", "revision": 8, "content_hash": "sha256:bd59f649091b89fd62a69c470b7912e7eefd770cc124746d00f1bfffbb857c6d", "created_at": "2026-11-01T15:40:53Z", "updated_at": "2026-11-01T22:01:04Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and Integrated Analysis of Key Biomarkers for Diagnosis and Prognosis of Non-Small Cell Lung Cancer.", "doi": "10.12659/MSM.918620", "pmid": "31805030", "authors": ["Xingyuan Liu", "Xuefeng Liu", "Jingyuan Li", "Fu Ren"], "journal": "Medical science monitor : international medical journal of experimental and clinical research", "year": 2019, "abstract": "Non-small cell lung cancer (NSCLC) is the main histologic form of lung cancer that affects human health, but biomarkers for therapeutic diagnosis and prognosis of the disease are currently lacking. The gene expression profile GSE18842 was downloaded from the Gene Expression Omnibus database in this prospective study, which consisted of 46 tumors and 45 controls. After screening differentially expressed genes (DEGs), we conducted functional enrichment analysis and KEGG analysis with upregulated differentially expressed genes (uDEGs) and downregulated differentially expressed genes (dDEGs), respectively. Protein-protein interaction (PPI) networks among DEGs and corresponding coding protein complexes, constructed using the STRING database, were analyzed using Cytoscape. Kaplan-Meier method was used to verify survival associated with hub genes. The GEPIA webserver was used to plot the gene expression level heat map of hub genes between NSCLC and adjacent lung tissues in the TCGA database. We identified 368 DEGs (168 uDEGs and 200 dDEGs) in NSCLC samples relative to control samples after gene integration. We established a PPI network for the DEGs, which had 249 nodes and 1472 edges protein pairs. Ten undefined hub genes with the highest connectivity degree (CDK1, UBE2C, AURKA, CCNA2, CDC20, CCNB1, TOP2A, ASPM, MAD2L1, and KIF11) were verified by survival analysis, and 9 of them were associated with poorer overall survival in NSCLC. The expression reliability of hub genes was verified by use of the GEPIA web tool. The results suggested that UBE2C, AURKA, CCNA2, CDC20, CCNB1, TOP2A, ASPM, MAD2L1, and KIF11 are inherent key biomarkers for diagnosis and prognosis, while KEGG analysis results showed the mitotic cell cycle pathway is a probable signaling pathway contributing to NSCLC progression. These genes could be promising biomarkers for diagnosis and provide a new approach for developing targeted therapeutic NSCLC drugs.", "claims": [{"id": "claim-method", "statement": "We investigated whether hub gene was associated with overall survival using Kaplan-Meier method and log-rank test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31805030", "locator": "sections[7] \"Survival analysis validation of hub genes\" paragraph 2", "quote": "We investigated whether hub gene was associated with overall survival using Kaplan-Meier method and log-rank test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The gene expression profile GSE18842 based on GPL570 (HG-U133_Plus_2) Affymetrix Human Genome U133 Plus 2.0 Array was downloaded from the NCBI GEO database (http://www.ncbi.nlm.nih.gov/geo/, National Center for Biotechnology Information, Gene Expression Omnibus), a public depository database of gene expression data [8].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31805030", "locator": "sections[3] \"Microarray data\" paragraph 2", "quote": "The gene expression profile GSE18842 based on GPL570 (HG-U133_Plus_2) Affymetrix Human Genome U133 Plus 2.0 Array was downloaded from the NCBI GEO database (http://www.ncbi.nlm.nih.gov/geo/, National Center for Biotechnology Information, Gene Expression Omnibus), a public depository database of gene expression data [8]."}], "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:31805030"], "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:GSE18842"], "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:GSE18842"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:31805030", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.12659/MSM.918620", "sha256": "sha256:a4b3a66a1d12fde0d749cdd93e601c32e2cfb137b3bd6a5fb5d73bc39eb1954e", "bytes": 34656, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.12659/MSM.918620", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC6911305", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE18842", "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=GSE18842", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE18842", "version": null, "note": "The gene expression profile GSE18842 based on GPL570 (HG-U133_Plus_2) Affymetrix Human Genome U133 Plus 2.0 Array was downloaded from the NCBI GEO database (http://www.ncbi.nlm.nih.gov/geo/, National Center for Biotechnology Information, Gene Expression Omnibus), a public depository database of gene expression data [8].", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The gene expression profile GSE18842 based on GPL570 (HG-U133_Plus_2) Affymetrix Human Genome U133 Plus 2.0 Array was downloaded from the NCBI GEO database (http://www.ncbi.nlm.nih.gov/geo/, National Center for Biotechnology Information, Gene Expression Omnibus), a public depository database of gene expression data [8].", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM466947", "GSM466948", "GSM466949", "GSM466950", "GSM466951", "GSM466952", "GSM466953", "GSM466954", "GSM466955", "GSM466956", "GSM466957", "GSM466958", "GSM466959", "GSM466960", "GSM466961", "GSM466962", "GSM466963", "GSM466964", "GSM466965", "GSM466966", "GSM466967", "GSM466968", "GSM466969", "GSM466970", "GSM466971", "GSM466972", "GSM466973", "GSM466974", "GSM466975", "GSM466976", "GSM466977", "GSM466978", "GSM466979", "GSM466980", "GSM466981", "GSM466982", "GSM466983", "GSM466984", "GSM466985", "GSM466986", "GSM466987", "GSM466988", "GSM466989", "GSM466990", "GSM466991", "GSM466992", "GSM466993", "GSM466994", "GSM466995", "GSM466996", "GSM466997", "GSM466998", "GSM466999", "GSM467000", "GSM467001", "GSM467002", "GSM467003", "GSM467004", "GSM467005", "GSM467006", "GSM467007", "GSM467008", "GSM467009", "GSM467010", "GSM467011", "GSM467012", "GSM467013", "GSM467014", "GSM467015", "GSM467016", "GSM467017", "GSM467018", "GSM467019", "GSM467020", "GSM467021", "GSM467022", "GSM467023", "GSM467024", "GSM467025", "GSM467026", "GSM467027", "GSM467028", "GSM467029", "GSM467030", "GSM467031", "GSM467032", "GSM467033", "GSM467034", "GSM467035", "GSM467036", "GSM467037"], "sample_count": 91, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Gene expression analysis of human lung cancer and control samples", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:31805030:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:4bc5ba9ed4ec242dc3d85d34b27f124adbeaf6dd82084309c3947801b671675d", "bytes": 3013, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#t1-medscimonit-25-9280", "version": null, "note": "GO function annotation of uDEGs and dDEGs associated with NSCLC (TOP 5).", "structure": {"pmcid": "PMC6911305", "section_index": 11, "section_title": "Functional and pathway terms enrichment analysis", "row_count": 33, "column_count": 6}, "table": {"label": "Table 1", "caption": "GO function annotation of uDEGs and dDEGs associated with NSCLC (TOP 5).", "rows": [["Category", "Term", "Involved in", "Count", "%", "PValue"], ["uDEGs"], ["GOTERM_BP_DIRECT", "GO: 0030216", "Keratinocyte differentiation", "6", "0.034227039", "1.02E-04"], ["GOTERM_BP_DIRECT", "GO: 0043066", "Negative regulation of apoptotic process", "6", "0.034227039", "0.029216325"], ["GOTERM_BP_DIRECT", "GO: 0000281", "Mitotic cytokinesis", "5", "0.028522533", "3.52E-05"], ["GOTERM_BP_DIRECT", "GO: 0018149", "Peptide cross-linking", "5", "0.028522533", "2.75E-04"], ["GOTERM_BP_DIRECT", "GO: 0007267", "Cell-cell signaling", "5", "0.028522533", "0.001218331"], ["GOTERM_CC_DIRECT", "GO: 0005737", "Cytoplasm", "38", "0.216771249", "1.22E-05"], ["GOTERM_CC_DIRECT", "GO: 0005634", "Nucleus", "30", "0.171135197", "0.00966858"], ["GOTERM_CC_DIRECT", "GO: 0016020", "Membrane", "15", "0.085567598", "0.002997772"], ["GOTERM_CC_DIRECT", "GO: 0030496", "Midbody", "9", "0.051340559", "2.37E-07"], ["GOTERM_CC_DIRECT", "GO: 0001533", "Cornified envelope", "5", "0.028522533", "9.17E-05"], ["GOTERM_MF_DIRECT", "GO: 0005198", "Structural molecule activity", "11", "0.062749572", "4.91E-07"], ["GOTERM_MF_DIRECT", "GO: 0005509", "Calcium ion binding", "13", "0.074158585", "0.001208322"], ["GOTERM_MF_DIRECT", "GO: 0005524", "ATP binding", "18", "0.102681118", "0.005172406"], ["GOTERM_MF_DIRECT", "GO: 0003777", "Microtubule motor activity", "4", "0.022818026", "0.006725855"], ["GOTERM_MF_DIRECT", "GO: 0008201", "Heparin binding", "4", "0.022818026", "0.030940109"], ["dDEGs"], ["GOTERM_BP_DIRECT", "GO: 0007155", "Cell adhesion", "10", "7.633587786", "0.00455356"], ["GOTERM_BP_DIRECT", "GO: 0006898", "Receptor-mediated endocytosis", "9", "6.870229008", "4.47E-05"], ["GOTERM_BP_DIRECT", "GO: 0006954", "Inflammatory response", "8", "6.106870229", "0.016151235"], ["GOTERM_BP_DIRECT", "GO: 0001525", "Angiogenesis", "6", "4.580152672", "0.019308307"], ["GOTERM_BP_DIRECT", "GO: 0007166", "Cell surface receptor signaling pathway", "6", "4.580152672", "0.041524321"], ["GOTERM_CC_DIRECT", "GO: 0005886", "Plasma membrane", "45", "34.35114504", "0.001297306"], ["GOTERM_CC_DIRECT", "GO: 0070062", "Extracellular exosome", "35", "26.71755725", "6.84E-04"], ["GOTERM_CC_DIRECT", "GO: 0005576", "Extracellular region", "31", "23.66412214", "4.61E-07"], ["GOTERM_CC_DIRECT", "GO: 0005615", "Extracellular space", "30", "22.90076336", "3.52E-08"], ["GOTERM_CC_DIRECT", "GO: 0005887", "Integral component of plasma membrane", "23", "17.55725191", "2.95E-04"], ["GOTERM_MF_DIRECT", "GO: 0008201", "Heparin binding", "6", "4.580152672", "0.003804314"], ["GOTERM_MF_DIRECT", "GO: 0030246", "Carbohydrate binding", "5", "3.816793893", "0.038241324"], ["GOTERM_MF_DIRECT", "GO: 0004888", "Transmembrane signaling receptor activity", "5", "3.816793893", "0.04997596"], ["GOTERM_MF_DIRECT", "GO: 0044325", "Ion channel binding", "4", "3.053435115", "0.036771904"], ["GOTERM_MF_DIRECT", "GO: 0005044", "Scavenger receptor activity", "3", "2.290076336", "0.038434779"]], "row_count": 33, "column_count": 6, "numeric_cells": 120, "header_rows": 1, "locator": "section[11]/table-wrap[1]#t1-medscimonit-25-9280"}}, {"id": "asset:table:pmid:31805030:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:359cdb2004fd7f7594fbdd43614699f9487b888b380c55afd642b41797e530cf", "bytes": 1120, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[2]#t2-medscimonit-25-9280", "version": null, "note": "KEGG pathway analysis of differentially expressed genes associated with NSCLC..", "structure": {"pmcid": "PMC6911305", "section_index": 11, "section_title": "Functional and pathway terms enrichment analysis", "row_count": 13, "column_count": 6}, "table": {"label": "Table 2", "caption": "KEGG pathway analysis of differentially expressed genes associated with NSCLC..", "rows": [["Category", "Term", "Involved in", "Count", "%", "P value"], ["uDEGs"], ["KEGG_PATHWAY", "hsa04110", "Cell cycle", "10", "0.057045", "5.05E-08"], ["KEGG_PATHWAY", "hsa04114", "Oocyte meiosis", "8", "0.045636", "4.70E-06"], ["KEGG_PATHWAY", "hsa04914", "Progesterone-mediated oocyte maturation", "6", "0.034227", "1.90E-04"], ["KEGG_PATHWAY", "hsa04115", "p53 signaling pathway", "5", "0.028523", "7.62E-04"], ["KEGG_PATHWAY", "hsa04512", "ECM-receptor interaction", "4", "0.022818", "0.016755"], ["dDEGs"], ["KEGG_PATHWAY", "hsa05144", "Malaria", "5", "3.816794", "8.27E-04"], ["KEGG_PATHWAY", "hsa03320", "PPAR signaling pathway", "5", "3.816794", "0.002661"], ["KEGG_PATHWAY", "hsa04610", "Complement and coagulation cascades", "4", "3.053435", "0.022"], ["KEGG_PATHWAY", "hsa05410", "Hypertrophic cardiomyopathy (HCM)", "4", "3.053435", "0.030239"], ["KEGG_PATHWAY", "hsa05143", "African trypanosomiasis", "3", "2.290076", "0.033223"]], "row_count": 13, "column_count": 6, "numeric_cells": 41, "header_rows": 1, "locator": "section[11]/table-wrap[2]#t2-medscimonit-25-9280"}}, {"id": "asset:table:pmid:31805030:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:9763e4d6e2857fb693bb3916087471b50b4b34756f3053a5b44d47908a1f5658", "bytes": 424, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#t3-medscimonit-25-9280", "version": null, "note": "Top 10 in network ranked by degree method.", "structure": {"pmcid": "PMC6911305", "section_index": 12, "section_title": "Protein–protein interaction (PPI) network construction and module analysis", "row_count": 11, "column_count": 3}, "table": {"label": "Table 3", "caption": "Top 10 in network ranked by degree method.", "rows": [["Rank", "Name", "Score"], ["1", "CDK1", "49"], ["2", "UBE2C", "48"], ["3", "AURKA", "47"], ["3", "CCNA2", "47"], ["5", "CDC20", "46"], ["5", "CCNB1", "46"], ["5", "TOP2A", "46"], ["5", "ASPM", "46"], ["9", "MAD2L1", "45"], ["9", "KIF11", "45"]], "row_count": 11, "column_count": 3, "numeric_cells": 22, "header_rows": 1, "locator": "section[12]/table-wrap[1]#t3-medscimonit-25-9280"}}], "gaps": ["asset:data:geo:GSE18842 not downloaded", "asset:data:geo:GSE18842 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "We investigated whether hub gene was associated with overall survival using Kaplan-Meier method and log-rank test."}}, {"id": "method-2", "family": "survival_analysis", "specific": "kaplan_meier", "label": "Survival analysis", "dsl_operations": ["survival_km"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.7, "band": "medium", "quote": "Kaplan-Meier"}}, {"id": "method-3", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "Protein-protein interaction"}}], "targets": [], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["logrank_test"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: log_rank_test."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE18842"], "resolved_accessions": ["GSE18842"], "statements": ["The gene expression profile GSE18842 based on GPL570 (HG-U133_Plus_2) Affymetrix Human Genome U133 Plus 2.0 Array was downloaded from the NCBI GEO database (http://www.ncbi.nlm.nih.gov/geo/, National Center for Biotechnology Information, Gene Expression Omnibus), a public depository database of gene expression data [8]."], "basis": "The paper names GSE18842 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["logrank_test"], "assets": ["source:pmid:31805030", "data:geo:GSE18842", "asset:table:pmid:31805030:1", "asset:table:pmid:31805030:2", "asset:table:pmid:31805030:3"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE18842"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:17:15Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 3, "usage": {"prompt_tokens": 27980, "completion_tokens": 1750, "cached_tokens": 784}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:31805030", "type": "paper", "label": "pmid:31805030"}, {"id": "source:pmid:31805030", "type": "manuscript", "label": "PMID 31805030 full text"}, {"id": "data:geo:GSE18842", "type": "dataset", "label": "GEO GSE18842"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:31805030", "type": "paper", "label": "pmid:31805030"}, {"id": "source:pmid:31805030", "type": "manuscript", "label": "PMID 31805030 full text"}, {"id": "data:geo:GSE18842", "type": "dataset", "label": "GEO GSE18842"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-31805030", "type": "extraction", "used": ["source:pmid:31805030"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE18842", "type": "accession_resolution", "used": ["data:geo:GSE18842"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:31805030", "parent_hash": "sha256:9b118639e1cec92e041491fc059f88908f5a8d097ef37c5d6a482949a99dbbe8", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE18842 licence not read", "asset:data:geo:GSE18842 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["logrank_test"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["We investigated whether hub gene was associated with overall survival using Kaplan-Meier method and log-rank test."], "order_basis": "analysis_only", "id": "assay:1"}]}