Identifying MMP14 and COL12A1 as a potential combination of prognostic biomarkers in pancreatic ductal adenocarcinoma using integrated bioinformatics analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33282565", "kind": "science-record", "revision": 7, "content_hash": "sha256:d880d683d7a31e38a3a043b56944866a8cbf36f608558506b85d45a92cf8fc29", "created_at": "2026-11-01T15:41:18Z", "updated_at": "2026-11-01T22:02:40Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identifying MMP14 and COL12A1 as a potential combination of prognostic biomarkers in pancreatic ductal adenocarcinoma using integrated bioinformatics analysis.", "doi": "10.7717/peerj.10419", "pmid": "33282565", "authors": ["Jingyi Ding", "Yanxi Liu", "Yu Lai"], "journal": "PeerJ", "year": 2020, "abstract": "BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignant neoplasm. It is necessary to improve the understanding of the underlying molecular mechanisms and identify the key genes and signaling pathways involved in PDAC.\nMETHODS: The microarray datasets GSE28735, GSE62165, and GSE91035 were downloaded from the Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified by integrated bioinformatics analysis, including protein-protein interaction (PPI) network, Gene Ontology (GO) enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The PPI network was established using the Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape software. GO functional annotation and KEGG pathway analyses were performed using the Database for Annotation, Visualization, and Integrated Discovery. Hub genes were validated via the Gene Expression Profiling Interactive Analysis tool (GEPIA) and the Human Protein Atlas (HPA) website.\nRESULTS: A total of 263 DEGs (167 upregulated and 96 downregulated) were common to the three datasets. We used STRING and Cytoscape software to establish the PPI network and then identified key modules. From the PPI network, 225 nodes and 803 edges were selected. The most significant module, which comprised 11 DEGs, was identified using the Molecular Complex Detection plugin. The top 20 hub genes, which were filtered by the CytoHubba plugin, comprised FN1, COL1A1, COL3A1, BGN, POSTN, FBN1, COL5A2, COL12A1, THBS2, COL6A3, VCAN, CDH11, MMP14, LTBP1, IGFBP5, ALB, CXCL12, FAP, MATN3, and COL8A1. These genes were validated using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, and the encoded proteins were subsequently validated using the HPA website. The GO analysis results showed that the most significantly enriched biological process, cellular component, and molecular function terms among the 20 hub genes were cell adhesion, proteinaceous extracellular matrix, and calcium ion binding, respectively. The KEGG pathway analysis showed that the 20 hub genes were mainly enriched in ECM-receptor interaction, focal adhesion, PI3K-Akt signaling pathway, and protein digestion and absorption. These findings indicated that FBN1 and COL8A1 appear to be involved in the progression of PDAC. Moreover, patient survival analysis performed via the GEPIA using TCGA and GTEx databases demonstrated that the expression levels of COL12A1 and MMP14 were correlated with a poor prognosis in PDAC patients (p < 0.05).\nCONCLUSIONS: The results demonstrated that upregulation of MMP14 and COL12A1 is associated with poor overall survival, and these might be a combination of prognostic biomarkers in PDAC.", "claims": [{"id": "claim-method", "statement": "Patient survival analysis performed via the GEPIA using TCGA and GTEx databases demonstrated that the high expression levels of COL12A1 and MMP14 were correlated with an unfavorable prognosis in PDAC patients (p < 0.05) (Fig. 5).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33282565", "locator": "sections[13] \"Overall survival analysis of the top 20 hub genes\" paragraph 2", "quote": "Patient survival analysis performed via the GEPIA using TCGA and GTEx databases demonstrated that the high expression levels of COL12A1 and MMP14 were correlated with an unfavorable prognosis in PDAC patients (p < 0.05) (Fig. 5)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The following information was supplied regarding data availability:\nThree microarray datasets are available at NCBI GEO: GSE28735, GSE62165, GSE91035. All the original figures and tables are available as Supplemental Files.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33282565", "locator": "sections[28] \"Data Availability Statement\" paragraphs 1-3", "quote": "The following information was supplied regarding data availability:\nThree microarray datasets are available at NCBI GEO: GSE28735, GSE62165, GSE91035. All the original figures and tables are available as Supplemental Files."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:33282565"], "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:GSE28735"], "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:GSE28735"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33282565", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7717/peerj.10419", "sha256": "sha256:f8a17c9bdb4ca94790b2a9d0f5070f50fc06763bf8f286db22e5b4007edc18fa", "bytes": 63405, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.7717/peerj.10419", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7690310", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE28735", "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=GSE28735", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE28735", "version": null, "note": "The following information was supplied regarding data availability:\nThree microarray datasets are available at NCBI GEO: GSE28735, GSE62165, GSE91035. 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All the original figures and tables are available as Supplemental Files.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The following information was supplied regarding data availability:\nThree microarray datasets are available at NCBI GEO: GSE28735, GSE62165, GSE91035. 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All the original figures and tables are available as Supplemental Files.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The following information was supplied regarding data availability:\nThree microarray datasets are available at NCBI GEO: GSE28735, GSE62165, GSE91035. All the original figures and tables are available as Supplemental Files.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2419974", "GSM2419975", "GSM2419976", "GSM2419977", "GSM2419978", "GSM2419979", "GSM2419980", "GSM2419981", "GSM2419982", "GSM2419983", "GSM2419984", "GSM2419985", "GSM2419986", "GSM2419987", "GSM2419988", "GSM2419989", "GSM2419990", "GSM2419991", "GSM2419992", "GSM2419993", "GSM2419994", "GSM2419995", "GSM2419996", "GSM2419997", "GSM2419998", "GSM2419999", "GSM2420000", "GSM2420001", "GSM2420002", "GSM2420003", "GSM2420004", "GSM2420005", "GSM2420006", "GSM2420007", "GSM2420008", "GSM2420009", "GSM2420010", "GSM2420011", "GSM2420012", "GSM2420013", "GSM2420014", "GSM2420015", "GSM2420016", "GSM2420017", "GSM2420018", "GSM2420019", "GSM2420020", "GSM2420021", "GSM2420022", "GSM2420023"], "sample_count": 50, "group_sizes": null, "group_sizes_basis": null, "platform": "22763", "taxon": "Homo sapiens", "title": "The gene expression signatures of human normal, benign and PDAC pancreatic tisssues.", "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:33282565:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:936f826d508e32db4c6166f57d070399663a14688498e6126e13a124fb343089", "bytes": 2324, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[1]#table-1", "version": null, "note": "A total of 263 DEGs were identified from the three microarray datasets, which consisted of 167 upregulated genes and 96 downregulated genes present in pancreatic ductal adenocarcinoma (PDAC) tissues in comparison with non-tumor tissues.", "structure": {"pmcid": "PMC7690310", "section_index": 10, "section_title": "Identification of DEGs", "row_count": 3, "column_count": 2}, "table": {"label": "Table 1", "caption": "A total of 263 DEGs were identified from the three microarray datasets, which consisted of 167 upregulated genes and 96 downregulated genes present in pancreatic ductal adenocarcinoma (PDAC) tissues in comparison with non-tumor tissues.", "rows": [["DEGs", "Gene names"], ["Upregulated", "XDH, RTKN2, PTPRR, ADAM12, STYK1, TPX2, PADI1, HEPH, CEACAM6, ITGA3, COL1A1, ANLN, FNDC1, PCDH7, SLC6A6, TRIM29, PXDN, EDNRA, LTBP1, MFAP5, PLA2R1, FN1, KRT17, PGM2L1, IFI27, ASAP2, LAMB3, TNFAIP6, HOXB5, OAS1, NTM, COL5A2, OSBPL3, TMPRSS4, ANTXR1, SDR16C5, OLR1, NT5E, CTSK, SULF2, MXRA5, APOL1, CDH11, AREG, MALL, S100A16, BGN, LAMA3, COL8A1, IGFBP5, MMP12, ADAMTS6, SLC2A1, CD109, ECT2, KIF23, MMP11, CDH3, LMO7, CCL18, ATP2C2, POSTN, MMP14, ADAM28, SRPX2, CEACAM5, TMC5, OAS2, MUC17, GABRP, COMP, SYTL2, GPX8, RUNX2, DLGAP5, KRT19, VCAN, MKI67, SULF1, LAMC2, GCNT3, NMU, MUC13, CEACAM1, ETV1, COL12A1, AGR2, ST6GALNAC1, SLC44A4, PLAU, S100P, SERPINB5, FOXQ1, TGM2, ITGB4, DCBLD2, TRIM31, RAI14, NRP2, SGIP1, CST1, ARNTL2, LEF1, MYOF, ANO1, S100A14, DDX60, KYNU, CAPG, CCL20, MATN3, NPR3, GPRC5A, NOX4, IL1RAP, ACSL5, HPGD, GREM1, SCEL, FBN1, IGFL2, SLC6A14, KRT6A, DHRS9, ANGPT2, MST1R, COL3A1, TMEM45B, EDIL3, ASPM, FAP, INPP4B, LOXL2, NQO1, CYP2C18, IFI44L, HK2, EFNB2, AEBP1, SLC16A3, CORIN, THBS2, BCAS1, DSG3, DKK1, RHBDL2, COL17A1, TSPAN1, FERMT1, CXCL5, COL6A3, COL10A1, ACTA2, PLAC8, AHNAK2, MLPH, FBXO32, TGFBI, KCNN4, CLDN18, FGD6, MTMR11, FXYD3, MBOAT2, SEMA3C, DPYSL3, CENPF"], ["Downregulated", "EPB41L4B, GSTA2, KIAA1324, CELA3A, ACADL, CEL, SLC39A5, LONRF2, SLC3A1, NRG4, MT1G, PROX1, G6PC2, C5, EGF, FAM3B, AQP8, CLPS, SLC17A4, CPB1, GP2, PDK4, RBPJL, PDIA2, PM20D1, CTRC, IAPP, PLA2G1B, ERP27, CELA2B, GRPR, REG1A, KIF1A, GUCA1C, CTRL, SYCN, CHRM3, TMED6, ALB, KCNJ16, REG3A, SLC4A4, AOX1, SERPINA5, CELA2A, SPINK1, FAM129A, FAM150B, SLC16A12, F11, CPA2, SV2B, BNIP3, C2CD4B, SLC1A2, REG1B, SCGN, PAK3, PRSS3, GRB14, REG3G, DCDC2, F8, GPHA2, EPHX2, PNLIPRP2, SLC7A2, CPA1, PRKAR2B, ONECUT1, BACE1, NUCB2, HOMER2, CXCL12, SLC43A1, GNMT, NR5A2, ALDH1A1, IL22RA1, BEX1, ANPEP, CFTR, FLRT2, LMO3, FGL1, NRCAM, FABP4, PNLIPRP1, KLK1, SERPINI2, GATM, DPP10, C6, SLC16A10, PRSS1, PAH"]], "row_count": 3, "column_count": 2, "numeric_cells": 2, "header_rows": 1, "locator": "section[10]/table-wrap[1]#table-1"}}, {"id": "asset:table:pmid:33282565:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:49c6cbaff8badbf88be2595d7674fcc54788f9644ca192190d97577041d38026", "bytes": 1559, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#table-2", "version": null, "note": "Results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the most significant module.", "structure": {"pmcid": "PMC7690310", "section_index": 12, "section_title": "GO and KEGG pathway analysis of DEGs", "row_count": 13, "column_count": 6}, "table": {"label": "Table 2", "caption": "Results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the most significant module.", "rows": [["Pathway ID", "Pathway description", "Count in gene set", "p-value", "FDR", "DEGs"], ["GO:0007155", "Cell adhesion", "5", "1.37E−06", "0.001121514", "COL6A3, COL12A1, VCAN, POSTN, THBS2"], ["GO:0001501", "Skeletal system development", "3", "3.80E−04", "0.310820683", "FBN1, VCAN, COL5A2"], ["GO:0030199", "Collagen fibril organization", "2", "0.017003019", "13.1195401", "COL5A2, CDH11"], ["GO:0005201", "Extracellular matrix structural constituent", "4", "2.39E−06", "0.001487027", "COL3A1, FBN1, VCAN, COL5A2"], ["GO:0005509", "Calcium ion binding", "4", "0.003312243", "2.045566581", "FBN1, VCAN, THBS2, CDH11"], ["GO:0005578", "Proteinaceous extracellular matrix", "6", "1.81E−08", "1.29E−05", "COL3A1, COL6A3, FBN1, COL12A1, VCAN, POSTN"], ["GO:0005581", "Collagen trimer", "3", "3.07E−04", "0.217600344", "COL3A1, COL6A3, COL12A1"], ["GO:0031012", "Extracellular matrix", "3", "0.001912518", "1.350246354", "FBN1, COL12A1, THBS2"], ["GO:0005615", "Extracellular space", "4", "0.008881226", "6.138544445", "COL6A3, FBN1, COL12A1, POSTN"], ["GO:0005604", "Basement membrane", "2", "0.032936583", "21.16653102", "FBN1, THBS2"], ["gga04512", "ECM–receptor interaction", "4", "4.51E−05", "0.019602271", "COL3A1, COL6A3, THBS2, COL5A2"], ["gga04510", "Focal adhesion", "4", "7.12E−04", "0.309146908", "COL3A1, COL6A3, THBS2, COL5A2"]], "row_count": 13, "column_count": 6, "numeric_cells": 55, "header_rows": 1, "locator": "section[12]/table-wrap[1]#table-2"}}, {"id": "asset:table:pmid:33282565:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:b95bb7176239915d59f07ed7eb449602383c84fcd3bf131060e6e77c4e845286", "bytes": 2602, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[2]#table-3", "version": null, "note": "Results of GO and KEGG pathway analyses of 20 hub genes.", "structure": {"pmcid": "PMC7690310", "section_index": 12, "section_title": "GO and KEGG pathway analysis of DEGs", "row_count": 24, "column_count": 6}, "table": {"label": "Table 3", "caption": "Results of GO and KEGG pathway analyses of 20 hub genes.", "rows": [["Pathway ID", "Pathway description", "Count in gene set", "p-value", "FDR", "DEGs"], ["GO:0007155", "Cell adhesion", "6", "3.07E−07", "3.44E−04", "COL12A1, POSTN, VCAN, COL8A1, THBS2, FN1"], ["GO:0035987", "Endodermal cell differentiation", "4", "6.17E−06", "0.006927836", "COL12A1, MMP14, COL8A1, FN1"], ["GO:0018149", "Peptide cross-linking", "2", "0.02230059", "22.35847168", "COL3A1, FN1"], ["GO:0043588", "Skin development", "2", "0.035457234", "33.30840338", "COL3A1, COL5A2"], ["GO:0030199", "Collagen fibril organization", "2", "0.035457234", "33.30840338", "COL3A1, COL5A2"], ["GO:0042060", "Wound healing", "2", "0.039805932", "36.60570116", "COL3A1, FN1"], ["GO:0001501", "Skeletal system development", "2", "0.048448486", "42.72191792", "FBN1, COL5A2"], ["GO:0005578", "Proteinaceous extracellular matrix", "7", "1.25E−08", "1.13E−05", "MATN3, BGN, FBN1, COL12A1, POSTN, COL1A1, FN1"], ["GO:0031012", "Extracellular matrix", "4", "1.37E−04", "0.123843274", "COL12A1, VCAN, MMP14, COL8A1"], ["GO:0005581", "Collagen trimer", "3", "7.87E−04", "0.70897958", "COL12A1, COL1A1, COL8A1"], ["GO:0005615", "Extracellular space", "6", "0.001248571", "1.122732142", "ALB, FAP, COL3A1, FBN1, COL12A1, VCAN"], ["GO:0005604", "Basement membrane", "3", "0.001310663", "1.178271997", "FBN1, COL8A1, THBS2"], ["GO:0001527", "Microfibril", "2", "0.008113224", "7.097635089", "LTBP1, FBN1"], ["GO:0070062", "Extracellular exosome", "7", "0.033863185", "26.75315613", "BGN, ALB, FBN1, COL12A1, COL8A1, FN1, CDH11"], ["GO:0005509", "Calcium ion binding", "7", "9.57E−06", "0.007173793", "MMP14, MATN3, LTBP1, FBN1, VCAN, THBS2, CDH11"], ["GO:0005201", "Extracellular matrix structural constituent", "3", "4.84E−04", "0.362368483", "COL3A1, FBN1, COL5A2"], ["GO:0008201", "Heparin binding", "3", "0.003684116", "2.728227814", "POSTN, THBS2, FN1"], ["ocu04512", "ECM–receptor interaction", "6", "5.00E−08", "4.15E−05", "COL3A1, COL6A3, COL1A1, COL5A2, THBS2, FN1"], ["ocu04510", "Focal adhesion", "6", "3.64E−06", "0.003011517", "COL3A1, COL6A3, COL1A1, COL5A2, THBS2, FN1"], ["ocu04974", "Protein digestion and absorption", "5", "8.69E−06", "0.007197854", "COL3A1, COL6A3, COL12A1, COL1A1, COL5A2"], ["ocu04151", "PI3K-Akt signaling pathway", "6", "3.26E−05", "0.026969277", "COL3A1, COL6A3, COL1A1, COL5A2, THBS2, FN1"], ["ocu05146", "Amoebiasis", "4", "3.54E−04", "0.292970736", "COL3A1, COL1A1, COL5A2, FN1"], ["ocu04611", "Platelet activation", "3", "0.012199259", "9.669074187", "COL3A1, COL1A1, COL5A2"]], 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"expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "pathway enrichment"}}, {"id": "method-3", "family": null, "specific": null, "label": "Overall survival analysis", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Patient survival analysis performed via the GEPIA using TCGA and GTEx databases demonstrated that the high expression levels of COL12A1 and MMP14 were correlated with an unfavorable prognosis in PDAC patients (p < 0.05) (Fig. 5)."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "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", 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE28735", "GSE62165", "GSE91035"], "resolved_accessions": ["GSE28735", "GSE62165", "GSE91035"], "statements": ["The following information was supplied regarding data availability:\nThree microarray datasets are available at NCBI GEO: GSE28735, GSE62165, GSE91035. All the original figures and tables are available as Supplemental Files."], "basis": "The paper names GSE28735, GSE62165, GSE91035 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. 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METHODS: The microarray datasets GSE28735, GSE62165, and GSE91035 we", "ds ratio. Supplementary Materials File S1The microarray datasets GSE28735 , GSE62165, and GSE9103510", "nal data file. Supplemental Information 3The microarray datasets GSE28735 , GSE62165, and GSE9103510"], "order_basis": "paper_text_order:363", "id": "assay:1"}, {"role": "analysis", "definition_id": "network_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.7, "evidence": ["protein-protein interaction"], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}