POLE2 Serves as a Prognostic Biomarker and Is Associated with Immune Infiltration in Squamous Cell Lung Cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32304567", "kind": "science-record", "revision": 8, "content_hash": "sha256:5df005c01d602c0074a29483db49dced29a6f4bebd535e2865deea4b7c3802f1", "created_at": "2026-11-01T15:40:59Z", "updated_at": "2026-11-01T22:01:30Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "POLE2 Serves as a Prognostic Biomarker and Is Associated with Immune Infiltration in Squamous Cell Lung Cancer.", "doi": "10.12659/MSM.921430", "pmid": "32304567", "authors": ["Zhen Wu", "Yue-Ming Wang", "Yu Dai", "Liang-An Chen"], "journal": "Medical science monitor : international medical journal of experimental and clinical research", "year": 2020, "abstract": "BACKGROUND Squamous cell lung cancer is the main cause of cancer-associated mortality. The discovery of promising prognostic biomarkers for predicting the survival of patients with squamous cell lung cancer remains a challenge. MATERIAL AND METHODS Gene expression profiles of GSE33479 and GSE51855, including 42 squamous cell lung cancer tissues and 17 normal tissues, from the GEO database were assessed to find common differentially expressed genes (DEGs) via the GEO2R online tool and Venn diagram software. Then, gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analyses were conducted. The key protein-protein interaction (PPI) network within those common DEGs was subsequently illustrated through a combination of Search Tool for Retrieval of Interacting Genes (STRING) and Cytoscape software. Finally, core genes associated with survival and levels of immune infiltration were demonstrated by the Kaplan-Meier plotter and Tumor Immune Estimation Resource (TIMER) online database, respectively. RESULTS In total, 483 DEGs were involved, including 216 upregulated genes enriched in \"cell division\", \"DNA replication\", and \"DNA repair pathway\" and 267 downregulated genes enriched in \"cell adhesion\", \"oxidation-reduction process\", and \"cell-cell signaling\". The 75 core genes were selected by Molecular Complex Detection applied in Cytoscape. Four genes - MND1, FOXM1, CDC6, and POLE2 - were found to be significantly associated with survival. Further analysis of the KEEG pathway and TIMER database revealed that only POLE2 was enriched in \"DNA replication\" and its higher expression was negatively associated with survival and immune infiltration. CONCLUSIONS Higher expression of POLE2 is a prognosis-related biomarker for worse survival and is negatively associated with immune infiltration in squamous cell lung cancer.", "claims": [{"id": "claim-method", "statement": "The strength of the relationship of gene expression with level of immune infiltration was evaluated via Pearson’s correlation using absolute values as follows: 0.80–1.0 is “very strong”, 0.60–0.79 is “strong”, 0.40–0.59 is “moderate”, 0.20–0.39 is “weak”, and 0.00–0.19 is “very weak” [29].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32304567", "locator": "sections[9] \"Statistical analysis\" paragraph 2", "quote": "The strength of the relationship of gene expression with level of immune infiltration was evaluated via Pearson’s correlation using absolute values as follows: 0.80–1.0 is “very strong”, 0.60–0.79 is “strong”, 0.40–0.59 is “moderate”, 0.20–0.39 is “weak”, and 0.00–0.19 is “very weak” [29]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Gene expression profiles of GSE33479 and GSE51855 in squamous cell lung cancer and normal lung tissues were downloaded from the GEO database. Microarray data of GSE33479 and GSE51855 were all assessed in GP6480 Platforms, which consisted of 14 squamous cell lung cancer tissues and 13 normal lung tissues and 28 squamous cell lung cancer tissues and 4 normal lung tissues, respectively.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32304567", "locator": "sections[3] \"Microarray data analysis\" paragraph 2", "quote": "Gene expression profiles of GSE33479 and GSE51855 in squamous cell lung cancer and normal lung tissues were downloaded from the GEO database. Microarray data of GSE33479 and GSE51855 were all assessed in GP6480 Platforms, which consisted of 14 squamous cell lung cancer tissues and 13 normal lung tissues and 28 squamous cell lung cancer tissues and 4 normal lung tissues, respectively."}], "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:32304567"], "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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"group_sizes": null, "group_sizes_basis": null, "platform": "7341;6480", "taxon": "Homo sapiens", "title": "Lung adenocarcinoma subtypes definable by lung development-related miRNA expression profiles in association with clinicopathologic features", "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:32304567:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:9b2a9b4425997fa8ab87884fc880895391639da8a554ad6bc7f833ec68f7d559", "bytes": 4069, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#t1-medscimonit-26-e921430", "version": null, "note": "All 483 commonly differentially expressed genes (DEGs) were collected from 3 profile datasets, including 216 upregulated genes and 267 downregulated genes in the squamous cell lung cancer tissues compared to normal tissues.", "structure": {"pmcid": "PMC7191965", "section_index": 11, "section_title": "Identification of DEGs in squamous cell lung cancer", "row_count": 3, "column_count": 2}, "table": {"label": "Table 1", "caption": "All 483 commonly differentially expressed genes (DEGs) were collected from 3 profile datasets, including 216 upregulated genes and 267 downregulated genes in the squamous cell lung cancer tissues compared to normal tissues.", "rows": [["DEGs", "Genes names"], ["Upregulated", "KRT16P2, ARHGAP11A, DEPDC1B, IGF2BP3, HOXD11, HRG, HOXC13, PKP1, NETO2, CALB1, CXCL13, HOXA13, LY6K, GPNMB, AKR1B10, GINS1, C16orf59, DUXAP8, ADAMDEC1, LOC399815, ANLN, BIRC5, CHRNA5, GJB6, KLK8, FOXM1, SPRR2D, CDK1, HIST1H3B, CHEK1, NEIL3, KIF11, PTHLH, KIF18B, ADAM23, AIM1L, POU4F1, CDC6, SAPCD2, CENPU, DSC2, MASTL, SMC4, KIF14, KIAA1549L, MAD2L1, NMRAL1P1, ARNTL2, CSTA, CARD14, PITX2, DEFB4A, RGS20, CENPL, ANKRD22, LINC01296, HOXA10, ARHGEF39, SPP1, SMCO2, CA9, LYPD3, MCM10, FAM83C, PPP2R2C, CASC9, FAM72D, TICRR, SOST, CENPA, TYMS, CDCA7, GRHL3, MELK, SFN, IL1RAP, ERC2, PRDM13, CENPN, IL36G, ZWINT, NDC80, SLC7A11, SGO1, GREM1, SPRR1A, PGLYRP4, KRT34, OIP5, CCNA2, IGFL2, ABCA12, BUB1, POLQ, NUF2, PBK, COCH, KRT6A, GNGT1, SKA1, MMP1, MMP12, CDCA5, UBE2T, CKS2, KIF23, DEPDC1, MMP11, FAM83A, CPA6, PLPP4, SKA3, TK1, DIAPH3, HOXC13-AS, TMEM158, HOXA11-AS, SPRR2C, MMP3, DSC3, CENPE, ZIC5, ASPM, PRSS2, ANXA10, KNL1, ATAD2, BRIP1, MND1, HOXD10, CCNB2, KRT6C, POLE2, MELTF, PIF1, CDT1, LRP8, FOXL2, POU6F2, CEP55, LINC01615, AUNIP, RRM2, KRT16, TOP2A, ERO1A, WDR72, ABCC5, FANCI, PLAC1, RAD54L, CCNE2, CDC45, S100A2, C6orf10, SPC25, CNTNAP2, KIF18A, WISP1, KIF15, KRT16P3, DSG3, BUB1B, LINC00659, DLGAP5, RAD51AP1, ZFP64, ESCO2, KRTAP4-1, IL36RN, MKI67, CLSPN, DTL, PTTG3P, ERVMER34-1, CDCA2, RAD51, AKR1C1, HMMR, HIST1H3D, SPRR3, CCDC150, C12orf56, CENPI, FBXO45, ERCC6L, JAKMIP3, AIM2, ORC6, S100A7, HOXC8, COL10A1, DEFB103B, KRT6B, COL11A1, LCAL1, PRAME, CTHRC1, UHRF1, FAM111B, KIAA0101, LHX2, KRT79, TTK, CDKN3, SH2D5, NCAPG, NEK2, GINS2, CENPF, NUSAP1, KRT75, ALPK2, SPRR1B, CDCA8"], ["Downregulated", "CHRDL1, ANGPTL5, UMODL1-AS1, MAATS1, WISP2, ITIH5, RGN, LGR6, FAT4, SLC22A4, NOSTRIN, SYNPO2, FLJ26850, PRR29, CYP2F1, NXPH3, CNN1, SAXO2, PLN, ANO5, LINC00261, CFAP206, HIF3A, CNTN4, C11orf88, SLC16A12, DACT3, PRDM16, GDF10, SEMA3E, ATOH8, TSPAN8, PPP1R9A, TNXB, PDZRN3, ANGPTL7, RSPH4A, EFHC1, LOC286191, STMND1, SMAD9, PIGR, RIIAD1, FOLR1, RCAN2, CAPN9, ITGA8, KRT222, SPATA4, SCRG1, SRD5A2, ZNF540, DUSP26, PTGFR, FHL1, C10orf107, C16orf71, DNALI1, PGM5-AS1, LEPR, PPP1R1B, RIC3, ABCA8, PPARGC1A, MFSD4A, ZFPM2, BHMT2, TMEM132C, FBLN1, TCF21, JPH2, RSPH1, LMOD1, ZBTB16, ELN, ADRA1B, DES, ASPA, CFAP43, MS4A8, EDNRB, RSPO1, UBXN10, HRCT1, ENKUR, SH3BGRL2, SPAG6, FAM81B, ARMC4, C1QTNF7, TRIM63, TMEM229A, ABI3BP, NRG2, WDR78, RUNDC3B, WIF1, C1QTNF2, SNCA, ROPN1L, ALDH7A1, CDHR3, PRUNE2, ERICH3, CRISP2, PIH1D3, NTRK3, C7, KHDRBS2, MORN5, NKX2-1, DYNLRB2, CSH1, C9orf135, PDK4, GPM6A, ACTN2, FILIP1, MAGI2-AS3, PDE1A, CPED1, FGF14, RERGL, PIFO, ANGPTL1, TMEM100, SLC22A3, HSD17B13, CAPN8, GREM2, ARHGAP20, CFAP70, NR3C2, EMCN, DPT, RGS5, ARMC3, GPIHBP1, EPHA3, MFAP4, ADGB, DRC3, DNAH7, OGN, SCARA5, PRG4, ATP1A2, ERICH2, DRC1, ADGRB3, CDO1, SDPR, ANOS1, SORBS1, PCDH20, ABCA6, SFTA3, LIFR, SGCA, EFHB, FGF9, PLCL1, LIMCH1, LRRC74B, AKAP12, C11orf97, MEOX2, SNTN, CXCL12, ADGRG2, APOD, ZNF880, PDE5A, NECAB1, MYOC, FMO5, PEG3-AS1, JAM2, DUSP27, KIAA1456, SPARCL1, SYNE1, RGS22, PDZRN4, TTC29, LINC01082, ZBBX, NME5, KCNA5, CACNB2, METTL7A, RHOJ, PGR, CCDC173, SRPX, SSTR1, FAM189A2, GPRASP1, C6orf118, SCN7A, SPATS1, PCDH9, CEP126, CAPSL, FLRT3, ZMYND12, LMO3, C9orf24, RBMS3, ACTG2, GNA14, SHANK2, SPAG8, TMEM213, IL33, C1orf194, ADH1B, ARHGAP6, KLF15, ME3, MYRIP, LINC00968, KCNB1, FAXDC2, CASC1, FAM107A, KCTD16, CDH19, LDLRAD1, CCBE1, DCDC5, PGM5, EYA4, FXYD1, PPP1R3C, ADAMTS9-AS2, ASB5, BMPR1B, SEMA5A, PI16, DAW1, SP5, LOC100506725, FAM47E, EFCAB1, CASQ2, SLIT2, HSPB7, WFDC1, FLJ30901, SCN2B, MACROD2, MAMDC2, ETV1, ADAMTSL3, ROR1, AR, MAPK4, CCDC178, GALNT16, LINC00472, DIO3OS, RNASE4, CYP4B1, PTGIS, WDR63"]], "row_count": 3, "column_count": 2, "numeric_cells": 2, "header_rows": 1, "locator": "section[11]/table-wrap[1]#t1-medscimonit-26-e921430"}}, {"id": "asset:table:pmid:32304567:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:1dacb08a221fff1176650ce7d506e27ed0d4fa76594beebf0e6f897a4943f228", "bytes": 2934, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#t2-medscimonit-26-e921430", "version": null, "note": "Gene ontology analysis of differentially expressed genes in squamous cell lung cancer.", "structure": {"pmcid": "PMC7191965", "section_index": 12, "section_title": "Analysis of GO and KEGG pathway in squamous cell lung cancer", "row_count": 31, "column_count": 7}, "table": {"label": "Table 2", "caption": "Gene ontology analysis of differentially expressed genes in squamous cell lung cancer.", "rows": [["Expression", "Category", "Term", "Count", "%", "p Value", "FDR"], ["Upregulated", "GOTERM_BP_DIRECT", "GO: 0051301 ~ cell division", "33", "15.28", "2.4E-21", "2.2E-18"], ["GOTERM_BP_DIRECT", "GO: 0007067 ~ mitotic nuclear division", "28", "12.96", "1.1E-19", "3.2E-17"], ["GOTERM_BP_DIRECT", "GO: 0007062 ~ sister chromatid cohesion", "22", "10.19", "2.4E-21", "2.2E-18"], ["GOTERM_BP_DIRECT", "GO: 0007059 ~ chromosome segregation", "15", "6.94", "1.2E-14", "2.7E-12"], ["GOTERM_BP_DIRECT", "GO: 0006260 ~ DNA replication", "15", "6.94", "1.2E-9", "2.3E-7"], ["GOTERM_BP_DIRECT", "GO: 0006281 ~ DNA repair", "14", "6.48", "1.5E-6", "1.8E-4"], ["GOTERM_CC_DIRECT", "GO: 0005634 ~ nucleus", "93", "43.06", "1.0E-7", "3.7E-6"], ["GOTERM_CC_DIRECT", "GO: 0005654 ~ nucleoplasm", "61", "28.24", "2.2E-8", "1.0E-6"], ["GOTERM_CC_DIRECT", "GO: 0005737 ~ cytoplasm", "75", "34.72", "2.2E-3", "1.9E-2"], ["GOTERM_CC_DIRECT", "GO: 0005829 ~ cytosol", "53", "24.54", "1.6E-3", "1.7E-2"], ["GOTERM_CC_DIRECT", "GO: 0005576 ~ extracellular region", "28", "12.96", "1.1E-2", "7.5E-2"], ["GOTERM_CC_DIRECT", "GO: 0043565 ~ extracellular space", "21", "9.72", "7.9E-2", "3.2E-1"], ["GOTERM_MF_DIRECT", "GO: 0005515 ~ protein binding", "126", "58.33", "3.4E-6", "4.5E-4"], ["GOTERM_MF_DIRECT", "GO: 0005524 ~ ATP binding", "32", "14.81", "3.0E-4", "1.6E-2"], ["GOTERM_MF_DIRECT", "GO: 0003677 ~ DNA binding", "25", "11.57", "9.1E-2", "6.8E-1"], ["GOTERM_MF_DIRECT", "GO: 0003682 ~ chromatin binding", "18", "8.33", "1.2E-6", "3.1E-4"], ["GOTERM_MF_DIRECT", "GO: 0005509 ~ calcium ion binding", "14", "6.48", "4.7E-2", "5.3E-1"], ["GOTERM_MF_DIRECT", "GO: 0043565 ~ sequence-specific DNA binding", "12", "5.56", "2.5E-2", "3.8E-1"], ["Downregulated", "GOTERM_BP_DIRECT", "GO: 0007155 ~ cell adhesion", "14", "5.24", "3.5E-3", "7.5E-1"], ["GOTERM_BP_DIRECT", "GO: 0055114 ~ oxidation-reduction process", "12", "4.49", "9.7E-2", "9.4E-1"], ["GOTERM_BP_DIRECT", "GO: 0007267 ~ cell-cell signaling", "9", "3.37", "1.1E-2", "7.4E-1"], ["GOTERM_BP_DIRECT", "GO: 0006936 ~ muscle contraction", "8", "3.00", "2.9E-4", "2.9E-1"], ["GOTERM_CC_DIRECT", "GO: 0005576 ~ extracellular region", "37", "13.86", "2.7E-4", "2.9E-2"], ["GOTERM_CC_DIRECT", "GO: 0043565 ~ extracellular space", "29", "10.86", "3.9E-3", "1.2E-1"], ["GOTERM_CC_DIRECT", "GO: 0005622 ~ intracellular", "26", "9.74", "2.1E-2", "3.0E-1"], ["GOTERM_CC_DIRECT", "GO: 0005578 ~ proteinaceous extracellular matrix", "14", "5.24", "2.6E-5", "5.8E-3"], ["GOTERM_MF_DIRECT", "GO: 0005509 ~ calcium ion binding", "23", "8.61", "3.2E-5", "1.2E-2"], ["GOTERM_MF_DIRECT", "GO: 0005102 ~ receptor binding", "9", "3.37", "5.4E-2", "7.8E-1"], ["GOTERM_MF_DIRECT", "GO: 0008201 ~ heparin binding", "10", "3.74", "1.1E-4", "2.0E-2"], ["GOTERM_MF_DIRECT", "GO: 0046983 ~ protein dimerization activity", "6", "2.24", "3.1E-2", "8.6E-1"]], "row_count": 31, "column_count": 7, "numeric_cells": 150, "header_rows": 1, "locator": "section[12]/table-wrap[1]#t2-medscimonit-26-e921430"}}, {"id": "asset:table:pmid:32304567:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:6fa5648542cadcbb9122ee28cae72a73df1453948a3b3786eab6fcb394efd030", "bytes": 643, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[2]#t3-medscimonit-26-e921430", "version": null, "note": "KEEG pathway analysis.", "structure": {"pmcid": "PMC7191965", "section_index": 12, "section_title": "Analysis of GO and KEGG pathway in squamous cell lung cancer", "row_count": 8, "column_count": 5}, "table": {"label": "Table 3", "caption": "KEEG pathway analysis.", "rows": [["Pathway ID", "Name", "Count", "%", "P value"], ["hsa04110", "Cell cycle", "13", "6.01", "2.0E-10"], ["hsa04115", "p53 signaling pathway", "6", "2.78", "2.0E-4"], ["hsa04114", "Oocyte meiosis", "6", "2.78", "2.0E-3"], ["hsa04914", "Progesterone-mediated oocyte maturation", "5", "2.31", "5.3E-3"], ["has03460", "Fanconi anemia pathway", "4", "1.85", "9.0E-3"], ["hsa04020", "Calcium signaling pathway", "6", "2.78", "3.7E-2"], ["has00240", "Pyrimidine metabolism", "4", "1.85", "4.9E-2"]], "row_count": 8, "column_count": 5, "numeric_cells": 29, "header_rows": 1, "locator": "section[12]/table-wrap[2]#t3-medscimonit-26-e921430"}}, {"id": "asset:table:pmid:32304567:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:a9cdf6cacc8b2518de4fe2eb28258b9c2e76943f9b3692361dd609ae22432682", "bytes": 887, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[14]/table-wrap[1]#t4-medscimonit-26-e921430", "version": null, "note": "The prognostic information of the 75 key candidate genes.", "structure": {"pmcid": "PMC7191965", "section_index": 14, "section_title": "Analysis of key genes by GEPIA and Kaplan-Meier plotter", "row_count": 3, "column_count": 2}, "table": {"label": "Table 4", "caption": "The prognostic information of the 75 key candidate genes.", "rows": [["Category", "Genes"], ["Genes predicting significantly worse survival (P<0.05)", "MND1, POLE2, CDC6, FOXM1"], ["Genes predicting significantly worse survival (P>0.05)", "KIF23, SKA3, SPC25, ATAD2, CDC45, CASC5, POLQ, CDK1, CCNA2, BIRC5, CDCA2, TTK, NDC80, ASPM, GINS2, CDKN3, TK1, CDT1, OIP5, DEPDC1, CCNB2, RAD54L, CEP55, NCAPG, DIAPH3, SKA1, NEIL3, CENPE, CDCA7, TYMS, KIF15, ANLN, CDCA5, CHEK1, NUF2, KIF18B, SGOL1, CKS2, MAD2L1, NUSAP1, BUB1, UHRF1, CENPN, HMMR, RAD51, KIF14, BUB1B, CDCA8, RRM2, ZWINT, DEPDC1B, KIF18A, FANCI, CENPU, NEK2, SMC4, PBK, ERCC6L, MKI67, MELK, KIF11, CENPF, MCM10, UBE2T, CENPA, RAD51AP1, KIAA0101, DLGAP5, DTL, ARHGAP11A, TOP2A"]], 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