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pmid:30697079
Integrated analysis of lncRNA-associated ceRNA network reveals potential biomarkers for the prognosis of hepatitis B virus-related hepatocellular carcinoma.
Hongyan Li · Xiaonan Zhao · Chenghua Li · Chuanlun Sheng · Zhenzi Bai
Cancer management and research · 2019 doi:10.2147/CMAR.S186561
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Complete file
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However, the mechanisms remain not fully elucidated. The study aimed to identify novel lncRNAs and explore their underlying mechanisms based on the ceRNA hypothesis.\nMETHODS: The RNA and miRNA expression profiling in 20 tumor and matched adjacent tissues from HBV-HCC patients were retrieved from the Gene Expression Omnibus database under accession numbers GSE77509 and GSE76903, respectively. Differentially expressed lncRNAs (DELs), miRNAs (DEMs), and genes (DEGs) were identified using the EdgeR package. Protein-protein interaction (PPI) network was constructed for DEGs followed by module analysis. The ceRNA network was constructed based on interaction relationships between miRNAs and mRNAs/lncRNAs. The functions of DEGs were predicted using DAVID and BinGO databases. The prognosis values (overall survival [OS] and recurrence-free survival [RFS]) of ceRNA network genes were determined using The Cancer Genome Atlas (TCGA) data with Cox regression analysis and Kaplan-Meier method.\nRESULTS: The present study screened 643 DELs, 83 DEMs, and 1,187 DEGs. PPI network analysis demonstrated that CDK1 and CCNE1 were hub genes and extracted in functionally related modules. E2F2, CDK1, and CCNE1 were significantly enriched into cell cycle pathway. FAM182B-miR-125b-5p-E2F2 and LINC00346-miR-10a-5p-CDK1/CCNE1 ceRNA axes were obtained by constructing the ceRNA network. Patients with high expressions of DELs and DEGs in the above ceRNA axes had poor OS, while patients with the high expression of DEMs possessed excellent OS. CDK1 was also an RFS-related biomarker, with its high expression predicting poor RFS. The upregulation of LINC00346 and CDK1 but the downregulation of miR-10a-5p in HCC was validated in other microarray datasets and TCGA database.\nCONCLUSION: The LINC00346-miR-10a-5p-CDK1 axis may be an important mechanism for HBV-related HCC, and genes in this ceRNA axis may be potential prognostic biomarkers and therapeutic targets.", "claims": [{"id": "claim-method", "statement": "Univariate Cox regression analysis was performed to screen prognosis-related DELs, DEMs, and DEGs using the survival package (Version 2.40.1; https://cran.r-project. org/package=survival). The Kaplan–Meier (KM) method with the log-rank test was employed to compare the overall survival (OS) and recurrence-free survival (RFS) between the high- and low-expression groups through the GraphPad Prism software (Version 5; GraphPad Software, Inc., La Jolla, CA, USA).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30697079", "locator": "sections[8] \"Prognosis values of DELs, DEMs, and DEGs in ceRNA network\" paragraph 2", "quote": "Univariate Cox regression analysis was performed to screen prognosis-related DELs, DEMs, and DEGs using the survival package (Version 2.40.1; https://cran.r-project. org/package=survival)."}, {"asset": "source:pmid:30697079", "locator": "sections[8] \"Prognosis values of DELs, DEMs, and DEGs in ceRNA network\" paragraph 2", "quote": "The Kaplan–Meier (KM) method with the log-rank test was employed to compare the overall survival (OS) and recurrence-free survival (RFS) between the high- and low-expression groups through the GraphPad Prism software (Version 5; GraphPad Software, Inc., La Jolla, CA, USA)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All the microarray data were downloaded from the GEO database in NCBI (http://www.ncbi.nlm.nih.gov/geo/). 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The mRNA and miRNA Seq-data were obtained from TCGA (https://tcga-data.nci.nih.gov/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1704144", "GSM1704145", "GSM1704146", "GSM1704147", "GSM1704148", "GSM1704149", "GSM1704150", "GSM1704151", "GSM1704152", "GSM1704153"], "sample_count": 10, "group_sizes": null, "group_sizes_basis": null, "platform": "10850", "taxon": "Homo sapiens", "title": "Differential miRNA expression profiles betweenHBV-related HCC tumor versus non-tumor liver tissue", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE76903", "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=GSE76903", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE76903", "version": null, "note": "All the microarray data were downloaded from the GEO database in NCBI (http://www.ncbi.nlm.nih.gov/geo/). The mRNA and miRNA Seq-data were obtained from TCGA (https://tcga-data.nci.nih.gov/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All the microarray data were downloaded from the GEO database in NCBI (http://www.ncbi.nlm.nih.gov/geo/). The mRNA and miRNA Seq-data were obtained from TCGA (https://tcga-data.nci.nih.gov/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2040356", "GSM2040357", "GSM2040358", "GSM2040359", "GSM2040360", "GSM2040361", "GSM2040362", "GSM2040363", "GSM2040364", "GSM2040365", "GSM2040366", "GSM2040367", "GSM2040368", "GSM2040369", "GSM2040370", "GSM2040371", "GSM2040372", "GSM2040373", "GSM2040374", "GSM2040375", "GSM2040376", "GSM2040377", "GSM2040378", "GSM2040379", "GSM2040380", "GSM2040381", "GSM2040382", "GSM2040383", "GSM2040384", "GSM2040385", "GSM2040386", "GSM2040387", "GSM2040388", "GSM2040389", "GSM2040390", "GSM2040391", "GSM2040392", "GSM2040393", "GSM2040394", "GSM2040395", "GSM2040396", "GSM2040397", "GSM2040398", "GSM2040399", "GSM2040400", "GSM2040401", "GSM2040402", "GSM2040403", "GSM2040404", "GSM2040405", "GSM2040406", "GSM2040407", "GSM2040408", "GSM2040409", "GSM2040410", "GSM2040411", "GSM2040412", "GSM2040413", "GSM2040414", "GSM2040415"], "sample_count": 60, "group_sizes": null, "group_sizes_basis": null, "platform": "16791", "taxon": "Homo sapiens", "title": "miRNA-seq analysis of hepatocellular carcinoma with portal vein tumor thrombosis", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE77509", "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=GSE77509", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE77509", "version": null, "note": "All the microarray data were downloaded from the GEO database in NCBI (http://www.ncbi.nlm.nih.gov/geo/). The mRNA and miRNA Seq-data were obtained from TCGA (https://tcga-data.nci.nih.gov/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All the microarray data were downloaded from the GEO database in NCBI (http://www.ncbi.nlm.nih.gov/geo/). The mRNA and miRNA Seq-data were obtained from TCGA (https://tcga-data.nci.nih.gov/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2053435", "GSM2053436", "GSM2053437", "GSM2053438", "GSM2053439", "GSM2053440", "GSM2053441", "GSM2053442", "GSM2053443", "GSM2053444", "GSM2053445", "GSM2053446", "GSM2053447", "GSM2053448", "GSM2053449", "GSM2053450", "GSM2053451", "GSM2053452", "GSM2053453", "GSM2053454", "GSM2053455", "GSM2053456", "GSM2053457", "GSM2053458", "GSM2053459", "GSM2053460", "GSM2053461", "GSM2053462", "GSM2053463", "GSM2053464", "GSM2053465", "GSM2053466", "GSM2053467", "GSM2053468", "GSM2053469", "GSM2053470", "GSM2053471", "GSM2053472", "GSM2053473", "GSM2053474", "GSM2053475", "GSM2053476", "GSM2053477", "GSM2053478", "GSM2053479", "GSM2053480", "GSM2053481", "GSM2053482", "GSM2053483", "GSM2053484", "GSM2053485", "GSM2053486", "GSM2053487", "GSM2053488", "GSM2053489", "GSM2053490", "GSM2053491", "GSM2053492", "GSM2053493", "GSM2053494"], "sample_count": 60, "group_sizes": null, "group_sizes_basis": null, "platform": "16791", "taxon": "Homo sapiens", "title": "RNA-seq analysis of hepatocellular carcinoma with portal vein tumor thrombosis", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE94660", "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=GSE94660", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE94660", "version": null, "note": "All the microarray data were downloaded from the GEO database in NCBI (http://www.ncbi.nlm.nih.gov/geo/). The mRNA and miRNA Seq-data were obtained from TCGA (https://tcga-data.nci.nih.gov/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All the microarray data were downloaded from the GEO database in NCBI (http://www.ncbi.nlm.nih.gov/geo/). The mRNA and miRNA Seq-data were obtained from TCGA (https://tcga-data.nci.nih.gov/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2480436", "GSM2480437", "GSM2480438", "GSM2480439", "GSM2480440", "GSM2480441", "GSM2480442", "GSM2480443", "GSM2480444", "GSM2480445", "GSM2480446", "GSM2480447", "GSM2480448", "GSM2480449", "GSM2480450", "GSM2480451", "GSM2480452", "GSM2480453", "GSM2480454", "GSM2480455", "GSM2480456", "GSM2480457", "GSM2480458", "GSM2480459", "GSM2480460", "GSM2480461", "GSM2480462", "GSM2480463", "GSM2480464", "GSM2480465", "GSM2480466", "GSM2480467", "GSM2480468", "GSM2480469", "GSM2480470", "GSM2480471", "GSM2480472", "GSM2480473", "GSM2480474", "GSM2480475", "GSM2480476", "GSM2480477"], "sample_count": 42, "group_sizes": null, "group_sizes_basis": null, "platform": "16791", "taxon": "Homo sapiens", "title": "RNA sequencing (RNA-SEQ) of 21 HBV-HCC patients with non-neoplastic liver and tumor tissues", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:30697079:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:7695dfbbc220c8418471147485147c10dc1ccd81885192d11d2599b19a1d89ca", "bytes": 1506, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[16]/table-wrap[1]#t8-cmar-11-877", "version": null, "note": "Confirmation of expressions of crucial lncRNAs, miRNAs, and mRNAs using other datasets", "structure": {"pmcid": "PMC6340501", "section_index": 9, "section_title": "Validation of expressions of crucial DELs, DEMs, and DEGs in ceRNA network", "row_count": 22, "column_count": 6}, "table": {"label": "Table 8", "caption": "Confirmation of expressions of crucial lncRNAs, miRNAs, and mRNAs using other datasets", "rows": [["RNA type", "Dataset", "Symbol", "Tumor (mean ± SD)", "Control (mean ± SD)", "P-value"], [""], ["lncRNA", "GSE27462", "FAM182B", "75.834±27.913", "71.793±23.127", "0.8096"], ["LINC00346", "124.665±28.955", "72.848±14.226", "0.01208"], ["TCGA", "FAM182B", "3.403±1.255", "2.539±0.944", "0.081"], ["LINC00346", "14.834±3.436", "12.679±1.403", "0.0397"], ["miRNA", "GSE69580", "miR-125b-5p", "39.384±23.416", "355.428±82.423", "0.000606"], ["miR-10a-5p", "4.229±2.103", "10.111±2.647", "0.00507"], ["TCGA", "miR-125b-5p", "8.962±1.092", "10.203±0.352", "4.09E–08"], ["miR-10a-5p", "13.607±1.198", "14.779±0.472", "4.89E–06"], ["mRNA", "GSE121248", "E2F2", "4.252±0.181", "4.239±0.157", "0.696"], ["CDK1", "7.224±1.105", "5.379±0.799", "2.68793E–16"], ["CCNE1", "7.056±1.032", "6.415±0.216", "0.00000344"], ["GSE94660", "E2F2", "0.83±0.443", "0.0611±0.028", "1.234E–07"], ["CDK1", "2.141±0.769", "0.251±0.121", "2.9E–10"], ["CCNE1", "1.412±0.669", "0.242±0.129", "9.01E–08"], ["GSE25599", "E2F2", "0.769±0.496", "0.302±0.255", "0.01958"], ["CDK1", "5.116±2.925", "1.152±0.923", "0.005978"], ["CCNE1", "2.015±1.820", "0.430±0.242", "0.02254"], ["TCGA", "E2F2", "5.612±1.296", "2.959±1.076", "0.000926"], ["CDK1", "8.018±1.428", "4.579±1.266", "0.00374"], ["CCNE1", "6.322±1.993", "3.162±0.979", "0.00193"]], "row_count": 22, "column_count": 6, "numeric_cells": 73, "header_rows": 1, "locator": "section[16]/table-wrap[1]#t8-cmar-11-877"}}, {"id": "asset:table:pmid:30697079:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:3bae17633ae76d5d181c9e11797747e02f2e70b847c9ef8e6c9d8bc0ec662226", "bytes": 2323, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#t1-cmar-11-877", "version": null, "note": "Differentially expressed genes, miRNAs, and lncRNAs", "structure": {"pmcid": "PMC6340501", "section_index": 11, "section_title": "Differential expression analysis", "row_count": 22, "column_count": 9}, "table": {"label": "Table 1", "caption": "Differentially expressed genes, miRNAs, and lncRNAs", "rows": [["Symbol", "LogFC", "FDR", "Symbol", "LogFC", "FDR", "Symbol", "LogFC", "FDR"], [""], ["CDC6", "1.05", "2.01E–03", "hsa-miR-215-3p", "29.41", "3.08E–06", "LINC01662", "4.62", "1.21E–07"], ["CCNE1", "1.02", "1.22E–02", "hsa-miR-301b", "3.80", "8.46E–11", "DSCR8", "4.49", "1.73E–17"], ["CDK1", "1.04", "2.02E–03", "hsa-miR-483-3p", "3.42", "3.40E–09", "LINC01976", "4.30", "7.43E–06"], ["E2F2", "1.03", "7.83E–03", "hsa-miR-410-3p", "3.25", "1.76E–08", "LINC00632", "3.70", "8.51E–13"], ["BUB1", "1.11", "6.22E–04", "hsa-miR-7974", "3.25", "3.05E–08", "DSCR4", "3.63", "2.03E–12"], ["CCNB1", "1.03", "2.17E–03", "hsa-miR-483-5p", "3.22", "2.62E–08", "LINC02089", "3.50", "9.85E–05"], ["SFN", "1.54", "4.46E–06", "hsa-miR-200c-3p", "3.17", "4.31E–08", "MIR2052HG", "3.34", "4.32E–11"], ["GNG4", "1.48", "6.54E–05", "hsa-miR-183-5p", "3.11", "6.10E–08", "PRNT", "2.54", "1.17E–03"], ["UBE2C", "1.23", "2.15E–04", "hsa-miR-1910-5p", "3.09", "4.44E–04", "LINC00346", "2.02", "3.33E–05"], ["GNGT1", "2.04", "1.49E–05", "hsa-miR-493-5p", "3.08", "8.66E–08", "FAM182B", "1.30", "1.04E–02"], ["KIF4A", "1.15", "5.96E–04", "hsa-miR-139-5p", "−2.22", "1.49E–04", "PACRG-AS3", "−1.24", "2.72E–02"], ["GNG13", "1.40", "1.87E–02", "hsa-miR-30c-2-3p", "−1.59", "1.04E–02", "LINC01558", "−1.59", "1.17E–03"], ["PF4", "−1.36", "2.03E–02", "hsa-miR-378i", "−1.54", "1.32E–02", "LINC02312", "−1.60", "1.47E–03"], ["IL-6", "−1.04", "2.94E–02", "hsa-miR-199a-5p", "−1.45", "2.11E–02", "LINC02453", "−1.74", "3.36E–04"], ["CXCR1", "−1.056", "1.64E–02", "hsa-miR-30a-5p", "−1.45", "2.16E–02", "LILRB1-AS1", "−1.87", "0.013104"], ["INS", "−3.6", "9.75E–11", "hsa-miR-125b-5p", "−1.43", "2.29E–02", "LINC01561", "−2.05", "7.28E–05"], ["RD3L", "−3.16", "2.70E–10", "hsa-miR-378d", "−1.43", "2.43E–02", "LINC01550", "−2.09", "1.89E–05"], ["VGLL1", "−2.96", "4.88E–06", "hsa-miR-10a-5p", "−1.41", "2.62E–02", "LINC01620", "−2.16", "2.77E–05"], ["TH", "−2.85", "7.02E–15", "hsa-miR-133a-3p", "−1.38", "3.15E–02", "LINC01554", "−2.19", "5.61E–06"], ["CLDN8", "−2.83", "3.13E–06", "hsa-miR-101-3p", "−1.37", "3.12E–02", "B3GALT5-AS1", "−2.31", "3.83E–06"]], "row_count": 22, "column_count": 9, "numeric_cells": 156, "header_rows": 1, "locator": "section[11]/table-wrap[1]#t1-cmar-11-877"}}, {"id": "asset:table:pmid:30697079:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:afeadb3928f6d00e1afaa3fe361569cfff9d0b6f2fe5c1863b78a1fe60e8318b", "bytes": 6057, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#t2-cmar-11-877", "version": null, "note": "GO enrichment for differentially expressed genes using the DAVID database", "structure": {"pmcid": "PMC6340501", "section_index": 12, "section_title": "Function enrichment for DEGs", "row_count": 22, "column_count": 4}, "table": {"label": "Table 2", "caption": "GO enrichment for differentially expressed genes using the DAVID database", "rows": [["Category", "Term", "FDR", "Genes"], [""], ["Up", "GO:0007049~cell cycle", "4.24E–10", "E2F1, KIF23, E2F2, KIFC1, XRCC2, E2F7, E2F8, MAEL, PKMYT1, TTK, PTTG1, AURKB, GTSE1, KIF2C, CCNE1, CDCA8, CDC45, CDCA2, PIWIL3, CDCA5, CDC6, CDK1, EGFL6, MND1, PBK, HMGA2, UBE2C, PRDM9, BUB1B, ERN2, NEK2, ANLN, CEP55, SPC24, SPC25, NCAPH, DUSP13, HJURP, NCAPG, CENPA, BUB1, FBXO43, SKA3, SKA1, TRIP13, EXO1, DLGAP5, NUF2, KIF18A, BIRC5, NDC80, CDC20, CDKN3, CDC25C, CDC25A, GSG2, CCNB1, CCNB2, TEX11"], ["GO:0022402~cell cycle process", "1.13E–11", "KIF23, E2F1, KIFC1, XRCC2, MAEL, PKMYT1, TTK, AURKB, PTTG1, GTSE1, CCNE1, KIF2C, CDCA8, CDCA2, PIWIL3, CDCA5, CDC6, CDK1, MND1, PBK, UBE2C, HMGA2, PRDM9, BUB1B, ERN2, NEK2, ANLN, CEP55, SPC24, SPC25, NCAPH, DUSP13, CENPA, NCAPG, FBXO43, BUB1, SKA3, SKA1, TRIP13, EXO1, DLGAP5, KIF18A, NUF2, NDC80, BIRC5, CDC20, CDC25C, CDKN3, CDC25A, CCNB1, CCNB2, TEX11"], ["GO:0022403~cell cycle phase", "1.74E–15", "E2F1, KIF23, KIFC1, XRCC2, NEK2, MAEL, TTK, PKMYT1, ANLN, PTTG1, CEP55, AURKB, GTSE1, SPC24, CCNE1, KIF2C, SPC25, NCAPH, CDCA8, DUSP13, NCAPG, BUB1, FBXO43, CDCA2, SKA3, PIWIL3, SKA1, CDCA5, TRIP13, EXO1, CDK1, CDC6, DLGAP5, NUF2, KIF18A, MND1, CDC20, BIRC5, NDC80, PBK, HMGA2, CDKN3, CDC25C, UBE2C, CDC25A, CCNB1, PRDM9, CCNB2, BUB1B, TEX11"], ["GO:0000279~M phase", "3.28E–16", "KIF23, KIFC1, XRCC2, NEK2, MAEL, TTK, PKMYT1, ANLN, PTTG1, CEP55, AURKB, SPC24, KIF2C, SPC25, NCAPH, CDCA8, DUSP13, NCAPG, BUB1, FBXO43, CDCA2, SKA3, PIWIL3, SKA1, CDCA5, TRIP13, EXO1, CDK1, CDC6, DLGAP5, NUF2, KIF18A, MND1, CDC20, BIRC5, NDC80, PBK, HMGA2, CDC25C, UBE2C, CDC25A, CCNB1, PRDM9, CCNB2, BUB1B, TEX11"], ["GO:0000278~mitotic cell cycle", "2.13E–11", "E2F1, KIF23, KIFC1, NEK2, TTK, PKMYT1, ANLN, PTTG1, CEP55, AURKB, GTSE1, SPC24, CCNE1, KIF2C, SPC25, CDCA8, NCAPH, NCAPG, CENPA, BUB1, CDCA2, SKA3, SKA1, CDCA5, CDK1, CDC6, DLGAP5, NUF2, KIF18A, CDC20, BIRC5, NDC80, PBK, HMGA2, CDKN3, CDC25C, UBE2C, CDC25A, CCNB1, CCNB2, BUB1B"], ["GO:0007067~mitosis", "6.55E–14", "KIF23, KIFC1, NEK2, PKMYT1, ANLN, CEP55, AURKB, PTTG1, SPC24, KIF2C, SPC25, CDCA8, NCAPH, NCAPG, BUB1, CDCA2, SKA3, SKA1, CDCA5, CDK1, CDC6, DLGAP5, NUF2, KIF18A, BIRC5, NDC80, CDC20, PBK, HMGA2, CDC25C, UBE2C, CDC25A, CCNB1, CCNB2, BUB1B"], ["GO:0000280~nuclear division", "6.55E–14", "KIF23, KIFC1, NEK2, PKMYT1, ANLN, CEP55, AURKB, PTTG1, SPC24, KIF2C, SPC25, CDCA8, NCAPH, NCAPG, BUB1, CDCA2, SKA3, SKA1, CDCA5, CDK1, CDC6, DLGAP5, NUF2, KIF18A, BIRC5, NDC80, CDC20, PBK, HMGA2, CDC25C, UBE2C, CDC25A, CCNB1, CCNB2, BUB1B"], ["GO:0000087~M phase of mitotic cell cycle", "9.83E–14", "KIF23, KIFC1, NEK2, PKMYT1, ANLN, CEP55, AURKB, PTTG1, SPC24, KIF2C, SPC25, CDCA8, NCAPH, NCAPG, BUB1, CDCA2, SKA3, SKA1, CDCA5, CDK1, CDC6, DLGAP5, NUF2, KIF18A, BIRC5, NDC80, CDC20, PBK, HMGA2, CDC25C, UBE2C, CDC25A, CCNB1, CCNB2, BUB1B"], ["GO:0048285~organelle fission", "1.97E–13", "KIF23, KIFC1, NEK2, PKMYT1, ANLN, CEP55, AURKB, PTTG1, SPC24, KIF2C, SPC25, CDCA8, NCAPH, NCAPG, BUB1, CDCA2, SKA3, SKA1, CDCA5, CDK1, CDC6, DLGAP5, NUF2, KIF18A, BIRC5, NDC80, CDC20, PBK, HMGA2, CDC25C, UBE2C, CDC25A, CCNB1, CCNB2, BUB1B"], ["GO:0051301~cell division", "2.47E–08", "KIF23, KIFC1, NEK2, ANLN, CEP55, AURKB, PTTG1, SPC24, CCNE1, SPC25, CDCA8, NCAPH, NCAPG, CDCA2, BUB1, SKA3, POU3F2, SKA1, CDCA5, CDK1, CDC6, NUF2, BIRC5, NDC80, CDC20, HMGA2, UBE2C, CDC25C, CDC25A, CCNB1, CCNB2, BUB1B"], ["Down", "GO:0007267~cell–cell signaling", "1.82E–07", "EDN3, GABRB3, FCRL2, VIPR1, VIPR2, GDNF, WNT2, KCNQ5, WISP2, SLC1A2, GRIN2B, CHRNA4, EFNB3, NPBWR1, IL26, NRXN1, NTSR1, IL22, SIGLEC6, GRM7, WNT9A, DRD1, GRAP, OXT, DRD5, TH, MME, RIMS1, CCL24, INS, CCL21, PRIMA1, BMP3, IL6, PLP1, NOS1, NTF3, DLGAP2, GABRA5, NPY5R, KCNK3, CCL17, WNT7B, CXCL14, PNOC, GRIA1, NTRK2, ADRA1A, SLC5A7, WNT7A, IL2, HTR2A"], ["GO:0006952~defense response", "2.83E–07", "KLRC4, KLRC2, KLRC3, CXCR1, CFP, GRIN2B, HAMP, RNASE7, IFNG, XCR1, NLRP7, CAMP, PRG2, PSG3, IL22, NCR1, NCR3, CCR9, PROK2, PSG8, PPBP, CD40LG, GRM7, DEFA3, PLA2G2D, CTSG, NGF, KIR3DL2, CLEC1B, C7, DRD1, CCK, CCL24, AZU1, FCN3, INS, CCL21, FCN2, CNR2, SFTPD, IL1RAPL2, SELP, IL6, IL5, IL1RL1, GABRA5, CCL19, CD5L, STAB2, S100A12, CCL17, MPO, SELE"], ["GO:0044057~regulation of system process", "3.67E–05", "BMP10, EDN3, DRD1, CCK, ERBB4, MYL3, EDN2, DRD5, OXT, TH, GDNF, DES, GRIN2B, INS, IFNG, LGI1, ARC, GNAO1, NOS1, NTF3, NPY1R, NPY5R, PROK2, TNNT3, CHRM2, NTRK2, TBXA2R, AVPR1A, IL2, HTR2A, NGF"], ["GO:0007268~synaptic transmission", "1.17E–04", "DRD1, GABRB3, DRD5, OXT, TH, VIPR1, RIMS1, WNT2, KCNQ5, SLC1A2, GRIN2B, CHRNA4, PRIMA1, PLP1, NOS1, NTF3, DLGAP2, NPBWR1, GABRA5, NRXN1, NTSR1, NPY5R, KCNK3, PNOC, GRIA1, GRM7, SLC5A7, WNT7A, HTR2A"], ["GO:0051046~regulation of secretion", "1.79E–03", "EDN3, IL6, EDN2, OXT, FGF23, NPY1R, GDNF, NPY5R, GCK, GRIN2B, CD40LG, INS, GRM7, IFNG, NTRK2, AVPR1A, CHRNA4, TRPV6, IL2, HTR2A, NGF"], ["GO:0006935ĉhemotaxis", "3.12E–03", "EDN3, IL6, EDN2, CXCR1, CCL19, PF4, CCL17, CCR9, AZU1, CCL24, PROK2, PPBP, CXCL14, CCL21, IFNG, SFTPD, XCR1, LECT2"], ["GO:0042742~defense response to bacterium", "8.64E–03", "SELP, IL6, CAMP, PRG2, STAB2, S100A12, AZU1, CFP, PPBP, HAMP, RNASE7, IFNG, DEFA3, CTSG"], ["GO:0050900~leukocyte migration", "9.20E–03", "AZU1, EDN3, SELP, IL6, EDN2, IFNG, ELANE, SFTPD, PF4, SELE"], ["GO:0022610~biological adhesion", "1.39E–02", "CLDN8, CLSTN2, OPCML, DSCAML1, CLDN10, L1CAM, MEGF10, WISP2, SRPX, TNR, DPT, DSCAM, TECTA, SELP, MAG, HAPLN4, RET, CDHR1, PCDH11X, CDHR2, IGFALS, SIGLEC11, AJAP1, STAB2, NRXN1, PCDH19, CTNNA3, CLEC4M, DSG4, LYVE1, FREM3, HEPACAM, SIGLEC6, FREM2, CD40LG, DSG1, CDH19, ITGAD, CNTN3, SELE, COL20A1, IL2"], ["GO:0006954înflammatory response", "2.80E–02", "SELP, C7, IL6, IL5, CXCR1, CCL19, IL22, S100A12, CCL17, NCR3, AZU1, CFP, CCL24, PROK2, FCN3, CD40LG, INS, CCL21, FCN2, CNR2, XCR1, SELE, PLA2G2D, NGF"]], "row_count": 22, "column_count": 4, "numeric_cells": 58, "header_rows": 1, "locator": "section[12]/table-wrap[1]#t2-cmar-11-877"}}, {"id": "asset:table:pmid:30697079:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:d2bbe71022ee8409ef83cdc5b8723cfd71624e1e5c40d15583674527b96400ad", "bytes": 2569, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[2]#t3-cmar-11-877", "version": null, "note": "KEGG pathway enrichment for differentially expressed genes using the DAVID database", "structure": {"pmcid": "PMC6340501", "section_index": 12, "section_title": "Function enrichment for DEGs", "row_count": 19, "column_count": 4}, "table": {"label": "Table 3", "caption": "KEGG pathway enrichment for differentially expressed genes using the DAVID database", "rows": [["Category", "Term", "FDR", "Genes"], [""], ["Up", "hsa04110:cell cycle", "2.16E–08", "E2F1, E2F2, CDK1, CDC6, PKMYT1, TTK, CDC20, PTTG1, SFN, CDC25C, CDC25A, CCNB1, CCNE1, CDC45, CCNB2, BUB1, BUB1B"], ["hsa04080:neuroactive ligand–receptor interaction", "2.66E–04", "GABRD, CGA, GABRG2, GABRA2, GABRA3, GLRA2, LEP, GRM4, SSTR5, KISS1R, HTR1B, GABRR1, GRID2, NPFFR2, TAAR1, HTR1D, GLP1R"], ["hsa04115:p53 signaling pathway", "2.08E–02", "CCNB1, CDK1, CCNE1, CCNB2, SFN, GTSE1"], ["hsa04060:cytokine–cytokine receptor interaction", "2.69E–02", "LEP, CCR8, CCL20, GDF5, EGF, BMP7, CCL7, IL11, CCL26"], ["hsa04062:chemokine signaling pathway", "2.73E–02", "CCR8, GNGT1, CCL20, GNG13, GNG4, CCL7, CCL26"], ["hsa00604:glycosphingolipid biosynthesis", "2.99E–02", "ST6GALNAC5, B4GALNT1"], ["hsa04512:ECM–receptor interaction", "3.14E–02", "IBSP, COMP, COL2A1, COL11A1"], ["hsa04350:TGF-beta signaling pathway", "3.33E–02", "COMP, GDF5, BMP7, PITX2"], ["hsa03320:PPAR signaling pathway", "4.83E–02", "LPL, MMP1, FABP6"], ["Down", "hsa00830:retinol metabolism", "8.15E–10", "CYP3A4, CYP1A1, CYP2B6, CYP2C8, ADH1B, CYP26A1, ADH7, CYP1A2, CYP3A43, CYP2A13, CYP4A11, UGT2B17, CYP4A22, LRAT, ADH4, CYP2A6, CYP2A7, RDH16"], ["hsa00982:drug metabolism", "2.89E–05", "CYP3A4, CYP2B6, CYP2C8, ADH1B, ADH7, CYP1A2, CYP2E1, GSTM5, CYP3A43, CYP2A13, UGT2B17, ADH4, CYP2A6, CYP2A7"], ["hsa04080:neuroactive ligand–receptor interaction", "1.79E–04", "GPR83, DRD1, GABRB3, DRD5, PTH1R, PRSS1, VIPR1, VIPR2, GCGR, GRIN2B, CNR2, GLP2R, GABRP, NPBWR1, GABRA5, NPY1R, NTSR1, NPY5R, GRIA1, CHRM2, GRM7, PTGDR, TBXA2R, AVPR1A, ADRA1A, CTSG, HTR2A"], ["hsa04060:cytokine–cytokine receptor interaction", "2.07E–04", "CXCR1, CNTFR, PF4, PF4V1, CCL24, CXCR5, CCL21, IFNG, XCR1, AMHR2, IL6, IL5, FLT3, TNFRSF13B, TNFRSF13C, IL26, CCL19, IL22, CCL17, CCR9, TSLP, CXCL14, PPBP, CD40LG, IL5RA, NGFR, IL2"], ["hsa00980:metabolism of xenobiotics by CYP/CYP450", "3.64E–04", "CYP3A43, CYP3A4, UGT2B17, CYP1A1, CYP2B6, ADH4, CYP2C8, ADH1B, ADH7, CYP2E1, CYP1A2, GSTM5"], ["hsa00232:caffeine metabolism", "1.50E–03", "CYP2A13, NAT2, CYP2A6, CYP2A7, CYP1A2"], ["hsa00983:drug metabolism", "2.10E–02", "CYP3A43, CYP3A4, CYP2A13, UGT2B17, NAT2, UPP2, CYP2A6, CYP2A7"], ["hsa04340:Hedgehog signaling pathway", "2.00E–02", "WNT2, WNT1, WNT10A, WNT7B, WNT9A, HHIP, GAS1, WNT7A, BMP5"]], "row_count": 19, "column_count": 4, "numeric_cells": 46, "header_rows": 1, "locator": "section[12]/table-wrap[2]#t3-cmar-11-877"}}, {"id": "asset:table:pmid:30697079:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:963d37d9ed400dfea629b2cc3f382ca151642bcc83c80e0411aa38862eca765e", "bytes": 2442, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#t4-cmar-11-877", "version": null, "note": "Topological features for each protein in PPI network", "structure": {"pmcid": "PMC6340501", "section_index": 13, "section_title": "PPI network construction", "row_count": 32, "column_count": 10}, "table": {"label": "Table 4", "caption": "Topological features for each protein in PPI network", "rows": [["Gene", "Degree", "Gene", "CC", "Gene", "BC", "Gene", "APL", "Overlapped", "Expression"], [""], ["GNGT1", "87", "IL6", "0.3179", "IL6", "0.2515", "IL6", "3.1461", "CCNB1", "Up"], ["GNG13", "85", "CHRM2", "0.2989", "UBE2C", "0.1845", "CHRM2", "3.3455", "CDK1", "Up"], ["GNG4", "64", "SH3GL2", "0.2959", "NGF", "0.1695", "SH3GL2", "3.3792", "GNG4", "Up"], ["CDK1", "56", "EGF", "0.2947", "TH", "0.1586", "EGF", "3.3933", "UBE2C", "Up"], ["CCNB1", "52", "ESR1", "0.2890", "GNGT1", "0.1413", "ESR1", "3.4607", "GNGT1", "Up"], ["CDC20", "48", "CCL20", "0.2848", "FOSB", "0.1406", "CCL20", "3.5112", "KIF4A", "Up"], ["BUB1", "48", "GNGT1", "0.2846", "MMP1", "0.1388", "GNGT1", "3.5140", "PF4", "Down"], ["CCNB2", "47", "GNG13", "0.2823", "CHRM2", "0.1186", "GNG13", "3.5421", "GNG13", "Up"], ["KIF2C", "47", "INS", "0.2821", "SH3GL2", "0.1164", "INS", "3.5449", "", ""], ["PMCH", "45", "UBE2C", "0.2808", "EGF", "0.1106", "UBE2C", "3.5618", "", ""], ["AURKB", "44", "PF4", "0.2803", "E2F1", "0.1043", "PF4", "3.5674", "", ""], ["CENPA", "43", "PTHLH", "0.2786", "ESR1", "0.1013", "PTHLH", "3.5899", "", ""], ["KIF20A", "39", "GNG4", "0.2777", "GNG13", "0.0956", "GNG4", "3.6011", "", ""], ["BUB1B", "39", "NGF", "0.2766", "INS", "0.0904", "NGF", "3.6152", "", ""], ["NCAPG", "38", "GNAO1", "0.2728", "KIF4A", "0.0670", "GNAO1", "3.6657", "", ""], ["CDCA8", "38", "KIF4A", "0.2722", "PTHLH", "0.0669", "KIF4A", "3.6742", "", ""], ["GCGR", "37", "PPBP", "0.2713", "CDK1", "0.0637", "PPBP", "3.6854", "", ""], ["NPSR1", "37", "GNA14", "0.2709", "ACAN", "0.0632", "GNA14", "3.6910", "", ""], ["BIRC5", "37", "LEP", "0.2707", "CCL20", "0.0620", "LEP", "3.6938", "", ""], ["TTK", "37", "TERT", "0.2707", "GNAO1", "0.0593", "TERT", "3.6938", "", ""], ["NDC80", "37", "GNAZ", "0.2669", "CAMK2B", "0.0547", "GNAZ", "3.7472", "", ""], ["DLGAP5", "36", "NGFR", "0.2661", "LPL", "0.0444", "NGFR", "3.7584", "", ""], ["UBE2C", "35", "SYT9", "0.2655", "CYP19A1", "0.0430", "SYT9", "3.7669", "", ""], ["CDC45", "35", "E2F1", "0.2651", "CCNB1", "0.0417", "E2F1", "3.7725", "", ""], ["PF4", "34", "HTR1B", "0.2645", "GNG4", "0.0402", "HTR1B", "3.7809", "", ""], ["KIF4A", "34", "CDK1", "0.2639", "CHRNA1", "0.0394", "CDK1", "3.7893", "", ""], ["PBK", "34", "PMCH", "0.2639", "PF4", "0.0393", "PMCH", "3.7893", "", ""], ["KIF23", "34", "HTR1D", "0.2639", "RHO", "0.0370", "HTR1D", "3.7893", "", ""], ["CXCR1", "33", "CCNB1", "0.2625", "NOS1", "0.0353", "CCNB1", "3.8090", "", ""], ["XCR1", "33", "CXCR1", "0.2597", "NGFR", "0.0348", "CXCR1", "3.8511", "", ""]], "row_count": 32, "column_count": 10, "numeric_cells": 136, "header_rows": 1, "locator": "section[13]/table-wrap[1]#t4-cmar-11-877"}}, {"id": "asset:table:pmid:30697079:6", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:8a7889e10452f86dccc0efd9a4e4eb98a92c04abc596da2893e78b18a9cbfdfd", "bytes": 6713, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[2]#t5-cmar-11-877", "version": null, "note": "BinGO enrichment for genes in modules", "structure": {"pmcid": "PMC6340501", "section_index": 13, "section_title": "PPI network construction", "row_count": 44, "column_count": 4}, "table": {"label": "Table 5", "caption": "BinGO enrichment for genes in modules", "rows": [["Module", "Description", "FDR", "Genes in test set"], [""], ["M1", "Mitotic cell cycle", "9.74E–37", "CDCA5|BUB1B|CDCA8|NCAPG|TTK|CENPA|SKA1|AUR KB|CDC20|CCNB2|CCNB1|PTTG1|NUF2|PBK|NEK2|BU B1|CEP55|DLGAP5|UBE2C|KIF23|NDC80|ANLN|KIF18 A|CDK1|BIRC5|KIF2C|SPC24|CDKN3|SPC25"], ["Nuclear division", "9.74E–37", "CDCA5|BUB1B|CDCA8|NCAPG|SKA1|AURKB|CDC20|C CNB2|CCNB1|PTTG1|NUF2|PBK|NEK2|BUB1|CEP55|D LGAP5|UBE2C|KIF23|NDC80|ANLN|KIF18A|CDK1|BIRC 5|KIF2C|SPC24|SPC25"], ["Mitosis", "9.74E–37", "CDCA5|BUB1B|CDCA8|NCAPG|SKA1|AURKB|CDC20|C CNB2|CCNB1|PTTG1|NUF2|PBK|NEK2|BUB1|CEP55|D LGAP5|UBE2C|KIF23|NDC80|ANLN|KIF18A|CDK1|BIRC 5|KIF2C|SPC24|SPC25"], ["M phase of mitotic cell cycle", "1.65E–36", "CDCA5|BUB1B|CDCA8|NCAPG|SKA1|AURKB|CDC20|C CNB2|CCNB1|PTTG1|NUF2|PBK|NEK2|BUB1|CEP55|D LGAP5|UBE2C|KIF23|NDC80|ANLN|KIF18A|CDK1|BIRC 5|KIF2C|SPC24|SPC25"], ["Organelle fission", "1.65E–36", "CDCA5|BUB1B|CDCA8|NCAPG|SKA1|AURKB|CDC20|C CNB2|CCNB1|PTTG1|NUF2|PBK|NEK2|BUB1|CEP55|D LGAP5|UBE2C|KIF23|NDC80|ANLN|KIF18A|CDK1|BIRC 5|KIF2C|SPC24|SPC25"], ["M phase", "2.75E–36", "CDCA5|BUB1B|CDCA8|NCAPG|TTK|SKA1|AURKB|CDC 20|CCNB2|CCNB1|PTTG1|NUF2|PBK|NEK2|BUB1|CEP 55|DLGAP5|UBE2C|KIF23|NDC80|ANLN|KIF18A|CDK1 |BIRC5|KIF2C|TRIP13|SPC24|SPC25"], ["Cell cycle phase", "1.03E–35", "CDCA5|BUB1B|CDCA8|NCAPG|TTK|SKA1|AURKB|CDC 20|CCNB2|CCNB1|PTTG1|NUF2|PBK|NEK2|BUB1|CEP 55|DLGAP5|UBE2C|KIF23|NDC80|ANLN|KIF18A|CDK1 |BIRC5|KIF2C|TRIP13|SPC24|CDKN3|SPC25"], ["Cell cycle process", "5.27E–34", "CDCA5|BUB1B|CDCA8|NCAPG|TTK|CENPA|SK A1|AURKB|CDC20|CCNB2|CCNB1|PTTG1|NUF 2|PBK|NEK2|BUB1|CEP55|DLGAP5|UBE2C|KIF 23|NDC80|ANLN|KIF18A|CDK1|BIRC5|KIF2C| TRIP13|SPC24|CDKN3|SPC25"], ["Cell cycle", "7.78E–34", "CDCA5|HJURP|BUB1B|CDCA8|NCAPG|TTK|CENPA|SK A1|AURKB|CDC20|CCNB2|CCNB1|CDC45|PTTG1|NU F2|PBK|NEK2|BUB1|CEP55|DLGAP5|UBE2C|KIF23|ND C80|ANLN|KIF18A|CDK1|BIRC5|KIF2C|TRIP13|SPC24| CDKN3|SPC25"], ["Cell division", "8.53E–28", "UBE2C|CDCA5|BUB1B|CDCA8|NCAPG|KIF23|SKA1|A URKB|NDC80|CDC20|CCNB2|ANLN|CCNB1|PTTG1| NUF2|CDK1|BIRC5|NEK2|KIF2C|BUB1|CEP55|SPC24 |SPC25"], ["M2", "G-protein-coupled receptor protein signaling pathway", "4.81E–36", "NPFFR2|CHRM2|PMCH|CXCR5|HTR2A|ADRA1A|GNGT 1|GNA14|GRM4|CXCR1|CNR2|TBXA2R|NPBWR1|KISS 1R|CCR9|CCR8|PROK2|TAC3|NTSR1|P2RY12|XCR1|ED N2|NPY5R|GCGR|HTR1D|NPY1R|HTR1B|CCK|AVPR1A| SSTR5|GNG13|PPYR1|PNOC"], ["Cell surface receptor-linked signaling pathway", "8.03E–26", "NPFFR2|CHRM2|PMCH|CXCR5|HTR2A|ADRA1A|GNGT 1|GNA14|GRM4|CXCR1|CNR2|TBXA2R|NPBWR1|KISS 1R|CCR9|CCR8|PROK2|TAC3|NTSR1|P2RY12|XCR1|ED N2|NPY5R|EDN3|GCGR|HTR1D|NPY1R|HTR1B|CCK|A VPR1A|SSTR5|GNG13|PPYR1|PNOC|PF4"], ["Signaling", "6.64E–24", "NPFFR2|CHRM2|PMCH|CXCR5|OXT|HTR2A|ADRA1A |GNGT1|GNA14|GRM4|CXCR1|CNR2|GRM7|TBXA2R| GNG4|NPBWR1|KISS1R|CCR9|CCR8|PROK2|TAC3|CCL 19|NTSR1|P2RY12|XCR1|EDN2|NPY5R|CCL21|EDN3| CCL20|GCGR|HTR1D|NPY1R|HTR1B|CCK|AVPR1A|SST R5|GNG13|APLN|PPYR1|PNOC|GNRH2|PF4"], ["Behavior", "1.44E–23", "PMCH|OXT|HTR2A|GRM4|CXCR1|CNR2|KISS1R|CCR 9|CCR8|PROK2|CCL19|NTSR1|XCR1|EDN2|NPY5R|C CL21|EDN3|CCL20|NPY1R|HTR1B|CCK|AVPR1A|PPBP |PPYR1|PF4"], ["Signaling pathway", "3.33E–20", "NPFFR2|CHRM2|PMCH|CXCR5|HTR2A|ADRA1A|GNGT 1|GNA14|GRM4|CXCR1|CNR2|TBXA2R|GNG4|NPBW R1|KISS1R|CCR9|CCR8|PROK2|TAC3|NTSR1|P2RY12|X CR1|EDN2|NPY5R|EDN3|GCGR|HTR1D|NPY1R|HTR1B |CCK|AVPR1A|SSTR5|GNG13|PPYR1|PNOC|PF4"], ["Signaling process", "2.04E–17", "CHRM2|PMCH|OXT|HTR2A|ADRA1A|GNGT1|GNA14| GRM4|CNR2|GRM7|NPBWR1|KISS1R|PROK2|CCL19|N TSR1|P2RY12|XCR1|EDN2|NPY5R|CCL21|EDN3|CCL2 0|GCGR|HTR1D|NPY1R|HTR1B|CCK|AVPR1A|SSTR5|G NG13|APLN|PNOC|GNRH2|PF4"], ["Signal transmission", "2.04E–17", "CHRM2|PMCH|OXT|HTR2A|ADRA1A|GNGT1|GNA14| GRM4|CNR2|GRM7|NPBWR1|KISS1R|PROK2|CCL19|N TSR1|P2RY12|XCR1|EDN2|NPY5R|CCL21|EDN3|CCL2 0|GCGR|HTR1D|NPY1R|HTR1B|CCK|AVPR1A|SSTR5|G NG13|APLN|PNOC|GNRH2|PF4"], ["Signal transduction", "1.43E–14", "CHRM2|PMCH|OXT|HTR2A|ADRA1A|GNGT1|GNA14| GRM4|CNR2|KISS1R|PROK2|CCL19|P2RY12|XCR1|ED N2|CCL21|EDN3|CCL20|GCGR|HTR1D|NPY1R|HTR1B| CCK|AVPR1A|SSTR5|GNG13|APLN|PNOC|GNRH2|PF4"], ["Response to stimulus", "2.05E–12", "NPFFR2|CHRM2|PMCH|OXT|HTR2A|ADRA1A|GNGT1| GRM4|CXCR1|CNR2|GRM7|GNG4|KISS1R|CCR9|CCR8 |PROK2|CCL19|NTSR1|P2RY12|XCR1|EDN2|NPY5R|C CL21|EDN3|CCL20|GCGR|HTR1D|NPY1R|HTR1B|CCK| AVPR1A|PPBP|GNG13|APLN|PPYR1|PF4"], ["Response to chemical stimulus", "2.96E–11", "XCR1|EDN2|CCL21|EDN3|CCL20|GCGR|HTR1D|NP Y1R|HTR1B|OXT|CCK|HTR2A|AVPR1A|PPBP|ADRA1A |GNG13|CXCR1|CNR2|GNG4|CCR9|CCR8|PROK2|CC L19|PF4"], ["M3", "Cyclic-nucleotide-mediated signaling", "6.43E–09", "GLP1R|VIPR1|GLP2R|PTH1R|DRD1|PTHLH|DRD5"], ["G-protein-coupled receptor protein signaling pathway", "2.93E–08", "VIPR1|GPR15|GLP2R|PTH1R|DRD1|TAAR1|PTHLH|DR D5|PTGDR"], ["Second messenger-mediated signaling", "9.78E–08", "GLP1R|VIPR1|GLP2R|PTH1R|DRD1|PTHLH|DRD5"], ["G-protein signaling, coupled to cyclic nucleotide second messenger", "9.78E–08", "VIPR1|GLP2R|PTH1R|DRD1|PTHLH|DRD5"], ["Cell surface receptor-linked signaling pathway", "2.27E–05", "VIPR1|GPR15|GLP2R|PTH1R|DRD1|TAAR1|PTHLH|DR D5|PTGDR"], ["Signaling", "3.01E–05", "GLP1R|VIPR1|GPR15|VIPR2|GLP2R|PTH1R|DRD1|CGA|T AAR1|PTHLH|DRD5|PTGDR"], ["Signaling pathway", "5.37E–05", "GLP1R|VIPR1|GPR15|GLP2R|PTH1R|DRD1|TAAR1|PTH LH|DRD5|PTGDR"], ["Intracellular signal transduction", "8.25E–05", "GLP1R|VIPR1|GLP2R|PTH1R|DRD1|PTHLH|DRD5"], ["Cell–cell signaling", "1.41E–04", "VIPR1|VIPR2|DRD1|CGA|PTHLH|DRD5"], ["Signal transduction", "1.59E–04", "GLP1R|VIPR1|VIPR2|GLP2R|PTH1R|DRD1|CGA|PTHLH |DRD5"], ["Signaling process", "4.51E–04", "GLP1R|VIPR1|VIPR2|GLP2R|PTH1R|DRD1|CGA|PTHLH |DRD5"], ["Cell communication", "7.10E–04", "VIPR1|VIPR2|DRD1|CGA|PTHLH|DRD5"], ["M4", "Drug metabolic process", "3.44E–16", "CYP2A6|CYP2C8|CYP2B6|CYP1A2|CYP1A1|CYP2E1|C YP3A4"], ["Secondary metabolic process", "4.89E–11", "CYP26A1|CYP2A6|CYP1A2|CYP1A1|CYP2E1|CYP3A4"], ["Oxidation reduction", "2.91E–10", "CYP26A1|CYP2A6|CYP2C8|CYP2B6|CYP4A11|CYP1A2|C YP1A1|CYP2E1|CYP3A4"], ["Steroid metabolic process", "4.84E–10", "CYP2A6|CYP2B6|CYP1A2|CYP1A1|UGT2B17|CYP2E1| CYP3A4"], ["Lipid metabolic process", "1.79E–09", "CYP26A1|CYP2A6|CYP2B6|CYP4A11|CYP1A2|CYP1A1| UGT2B17|CYP2E1|CYP3A4"], ["Response to drug", "1.12E–07", "CYP2A6|CYP2C8|CYP2B6|CYP1A2|CYP1A1|CYP3A4"], ["Cellular catabolic process", "2.17E–06", "CYP26A1|CYP2A6|CYP2C8|CYP2B6|CYP1A2|CYP1A1| CYP3A4"], ["Small molecule metabolic process", "3.78E–06", "CYP26A1|CYP2A6|CYP2C8|CYP2B6|CYP4A11|CYP1A2| CYP1A1|CYP3A4"], ["Cellular lipid metabolic process", "6.87E–06", "CYP26A1|CYP4A11|CYP1A2|CYP1A1|CYP2E1|CYP3A4"], ["Catabolic process", "9.30E–06", "CYP26A1|CYP2A6|CYP2C8|CYP2B6|CYP1A2|CYP1A1| CYP3A4"]], "row_count": 44, "column_count": 4, "numeric_cells": 74, "header_rows": 1, "locator": "section[13]/table-wrap[2]#t5-cmar-11-877"}}, {"id": "asset:table:pmid:30697079:7", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:8720a5dad12fc033cbf66457256206fe695ffd3d3f5eb732b4ad205b94d543a3", "bytes": 522, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[14]/table-wrap[1]#t6-cmar-11-877", "version": null, "note": "KEGG pathways for genes in ceRNA network", "structure": {"pmcid": "PMC6340501", "section_index": 14, "section_title": "CeRNA network construction", "row_count": 6, "column_count": 3}, "table": {"label": "Table 6", "caption": "KEGG pathways for genes in ceRNA network", "rows": [["Term", "P-value", "Genes"], [""], ["hsa04110:cell cycle", "2.85E–06", "CCNB1, E2F2, CDK1, CCNE1, CDC6, BUB1, SFN"], ["hsa04115:p53 signaling pathway", "0.001617", "CCNB1, CDK1, CCNE1, SFN"], ["hsa04080:neuroactive ligand–receptor interaction", "0.04606", "GPR83, GABRB3"], ["hsa05200:pathways in cancer", "0.046995", "E2F2, CCNE1"]], "row_count": 6, "column_count": 3, "numeric_cells": 9, "header_rows": 1, "locator": "section[14]/table-wrap[1]#t6-cmar-11-877"}}, {"id": "asset:table:pmid:30697079:8", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:ddb38bf1d20056e74c7a2d16466b887fcf58d0281bb88430e939a9394eb47be6", "bytes": 969, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[15]/table-wrap[1]#t7-cmar-11-877", "version": null, "note": "Cox regression analysis to screen survival-related genes", "structure": {"pmcid": "PMC6340501", "section_index": 15, "section_title": "Prognosis prediction for DELs, DEMs, and DEGs", "row_count": 19, "column_count": 5}, "table": {"label": "Table 7", "caption": "Cox regression analysis to screen survival-related genes", "rows": [["ID", "Overall survival", "Recurrence-free survival"], [""], ["", "HR", "P-value", "HR", "P-value"], [""], ["E2F2", "1.24", "0.049", "1.19", "0.16"], ["CDC6", "1.28", "0.0372", "1.41", "0.0099"], ["CCNE1", "1.05", "0.0456", "1.08", "0.32"], ["CDK1", "1.32", "0.022", "1.48", "0.0036"], ["BUB1", "1.31", "0.013", "1.37", "0.0054"], ["CCNB1", "1.4", "0.014", "1.36", "0.023"], ["SFN", "1.22", "0.0023", "1.19", "0.0055"], ["hsa-miR-10a-5p", "0.882", "0.04", "0.854", "0.27"], ["hsa-miR-125b-5p", "0.835", "0.019", "0.952", "0.74"], ["hsa-miR-133a-3p", "0.11", "0.045", "0.879", "0.39"], ["hsa-miR-199a-5p", "0.986", "0.88", "0.907", "0.28"], ["hsa-miR-30a-5p", "0.911", "0.0452", "0.866", "0.32"], ["LINC00346", "1.67", "0.0051", "0.99", "0.85"], ["DSCR4", "1.03", "0.68", "0.994", "0.95"], ["FAM182B", "1.152", "0.047", "0.84", "0.19"]], "row_count": 19, "column_count": 5, "numeric_cells": 67, "header_rows": 3, "locator": "section[15]/table-wrap[1]#t7-cmar-11-877"}}, {"id": "asset:table:pmid:30697079:9", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:7695dfbbc220c8418471147485147c10dc1ccd81885192d11d2599b19a1d89ca", "bytes": 1506, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[16]/table-wrap[1]#t8-cmar-11-877", "version": null, "note": "Confirmation of expressions of crucial lncRNAs, miRNAs, and mRNAs using other datasets", "structure": {"pmcid": "PMC6340501", "section_index": 16, "section_title": "Validation of expressions of crucial DELs, DEMs, and DEGs in ceRNA network", "row_count": 22, "column_count": 6}, "table": {"label": "Table 8", "caption": "Confirmation of expressions of crucial lncRNAs, miRNAs, and mRNAs using other datasets", "rows": [["RNA type", "Dataset", "Symbol", "Tumor (mean ± SD)", "Control (mean ± SD)", "P-value"], [""], ["lncRNA", "GSE27462", "FAM182B", "75.834±27.913", "71.793±23.127", "0.8096"], ["LINC00346", "124.665±28.955", "72.848±14.226", "0.01208"], ["TCGA", "FAM182B", "3.403±1.255", "2.539±0.944", "0.081"], ["LINC00346", "14.834±3.436", "12.679±1.403", "0.0397"], ["miRNA", "GSE69580", "miR-125b-5p", "39.384±23.416", "355.428±82.423", "0.000606"], ["miR-10a-5p", "4.229±2.103", "10.111±2.647", "0.00507"], ["TCGA", "miR-125b-5p", "8.962±1.092", "10.203±0.352", "4.09E–08"], ["miR-10a-5p", "13.607±1.198", "14.779±0.472", "4.89E–06"], ["mRNA", "GSE121248", "E2F2", "4.252±0.181", "4.239±0.157", "0.696"], ["CDK1", "7.224±1.105", "5.379±0.799", "2.68793E–16"], ["CCNE1", "7.056±1.032", "6.415±0.216", "0.00000344"], ["GSE94660", "E2F2", "0.83±0.443", "0.0611±0.028", "1.234E–07"], ["CDK1", "2.141±0.769", "0.251±0.121", "2.9E–10"], ["CCNE1", "1.412±0.669", "0.242±0.129", "9.01E–08"], ["GSE25599", "E2F2", "0.769±0.496", "0.302±0.255", "0.01958"], ["CDK1", "5.116±2.925", "1.152±0.923", "0.005978"], ["CCNE1", "2.015±1.820", "0.430±0.242", "0.02254"], ["TCGA", "E2F2", "5.612±1.296", "2.959±1.076", "0.000926"], ["CDK1", "8.018±1.428", "4.579±1.266", "0.00374"], ["CCNE1", "6.322±1.993", "3.162±0.979", "0.00193"]], "row_count": 22, "column_count": 6, "numeric_cells": 73, "header_rows": 1, "locator": "section[16]/table-wrap[1]#t8-cmar-11-877"}}], "gaps": ["asset:data:geo:GSE121248 not downloaded", "asset:data:geo:GSE121248 licence not read", "asset:data:geo:GSE25599 not downloaded", "asset:data:geo:GSE25599 licence not read", "asset:data:geo:GSE27462 not downloaded", "asset:data:geo:GSE27462 licence not read", "asset:data:geo:GSE69580 not downloaded", "asset:data:geo:GSE69580 licence not read", "asset:data:geo:GSE76903 not downloaded", "asset:data:geo:GSE76903 licence not read", "asset:data:geo:GSE77509 not downloaded", "asset:data:geo:GSE77509 licence not read", "asset:data:geo:GSE94660 not downloaded", "asset:data:geo:GSE94660 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "reordered", "quote": "Univariate Cox regression analysis was performed to screen prognosis-related DELs, DEMs, and DEGs using the survival package (Version 2.40.1; https://cran.r-project. org/package=survival). The Kaplan–Meier (KM) method with the log-rank test was employed to compare the overall survival (OS) and recurrence-free survival (RFS) between the high- and low-expression groups through the GraphPad Prism software (Version 5; GraphPad Software, Inc., La Jolla, CA, USA)."}}, {"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": "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": 0.8, "band": "high", "quote": "log-rank"}}, {"id": "method-4", "family": "differential_expression", "specific": "edger", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 0.7, "band": "medium", "quote": "EdgeR"}}, {"id": "method-5", "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": ["cox_ph"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: cox_proportional_hazards."}, "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": ["GSE77509", "GSE76903", "GSE121248", "GSE94660", "GSE25599", "GSE69580", "GSE27462"], "resolved_accessions": ["GSE77509", "GSE76903", "GSE121248", "GSE94660", "GSE25599", "GSE69580", "GSE27462"], "statements": ["All the microarray data were downloaded from the GEO database in NCBI (http://www.ncbi.nlm.nih.gov/geo/). The mRNA and miRNA Seq-data were obtained from TCGA (https://tcga-data.nci.nih.gov/)."], "basis": "The paper names GSE77509, GSE76903, GSE121248, GSE94660, GSE25599, GSE69580, GSE27462 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. 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CONCLUSION: The", "s Availability of data and materials All the microarray data were downloaded from the GEO database i"], "order_basis": "paper_text_order:1997", "id": "assay:1"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Univariate Cox regression analysis was performed to screen prognosis-related DELs, DEMs, and DEGs using the survival package (Version 2.40.1; https://cran.r-project. org/package=survival). The Kaplan–Meier (KM) method with the log-rank test was employed to compare the overall survival (OS) and recurrence-free survival (RFS) between the high- and low-expression groups through the GraphPad Prism software (Version 5; GraphPad Software, Inc., La Jolla, CA, USA)."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}