Bioinformatics analysis of differentially expressed genes and pathways in the development of cervical cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34174849", "kind": "science-record", "revision": 7, "content_hash": "sha256:687ea3ada1826eeae67562b89f21a69bbe9e7a702509014ae59dde88b5c13038", "created_at": "2026-11-01T15:41:40Z", "updated_at": "2026-11-01T22:04:01Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Bioinformatics analysis of differentially expressed genes and pathways in the development of cervical cancer.", "doi": "10.1186/s12885-021-08412-4", "pmid": "34174849", "authors": ["Baojie Wu", "Shuyi Xi"], "journal": "BMC cancer", "year": 2021, "abstract": "BACKGROUND: This study aimed to explore and identify key genes and signaling pathways that contribute to the progression of cervical cancer to improve prognosis.\nMETHODS: Three gene expression profiles (GSE63514, GSE64217 and GSE138080) were screened and downloaded from the Gene Expression Omnibus database (GEO). Differentially expressed genes (DEGs) were screened using the GEO2R and Venn diagram tools. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Gene set enrichment analysis (GSEA) was performed to analyze the three gene expression profiles. Moreover, a protein-protein interaction (PPI) network of the DEGs was constructed, and functional enrichment analysis was performed. On this basis, hub genes from critical PPI subnetworks were explored with Cytoscape software. The expression of these genes in tumors was verified, and survival analysis of potential prognostic genes from critical subnetworks was conducted. Functional annotation, multiple gene comparison and dimensionality reduction in candidate genes indicated the clinical significance of potential targets.\nRESULTS: A total of 476 DEGs were screened: 253 upregulated genes and 223 downregulated genes. DEGs were enriched in 22 biological processes, 16 cellular components and 9 molecular functions in precancerous lesions and cervical cancer. DEGs were mainly enriched in 10 KEGG pathways. Through intersection analysis and data mining, 3 key KEGG pathways and related core genes were revealed by GSEA. Moreover, a PPI network of 476 DEGs was constructed, hub genes from 12 critical subnetworks were explored, and a total of 14 potential molecular targets were obtained.\nCONCLUSIONS: These findings promote the understanding of the molecular mechanism of and clinically related molecular targets for cervical cancer.", "claims": [{"id": "claim-method", "statement": "The GEO2R tool was used to analyze the three expression datasets [6, 7]. Normalization and log2 conversion were carried out for each dataset to filter out the DEGs of the three datasets, and the DEGs are displayed as volcano plots. The filtering conditions were as follows: |log2-fold change| ≥ 1 and adjusted P-value (adj. P) < 0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34174849", "locator": "sections[4] \"Analysis of microarray datasets\" paragraph 2", "quote": "The GEO2R tool was used to analyze the three expression datasets [6, 7]. Normalization and log2 conversion were carried out for each dataset to filter out the DEGs of the three datasets, and the DEGs are displayed as volcano plots. The filtering conditions were as follows: |log2-fold change| ≥ 1 and adjusted P-value (adj. P) < 0.05."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The raw data of the three microarray datasets (accession numbers GSE63514, GSE64217 and GSE138080) were downloaded from the GEO repository (https://www.ncbi.nlm.nih.gov/geo/). All data are publicly accessible.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34174849", "locator": "sections[25] \"Availability of data and materials\" paragraph 2", "quote": "The raw data of the three microarray datasets (accession numbers GSE63514, GSE64217 and GSE138080) were downloaded from the GEO repository (https://www.ncbi.nlm.nih.gov/geo/). All data are publicly accessible."}], "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:34174849"], "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:GSE138080"], "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:GSE138080"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34174849", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12885-021-08412-4", "sha256": "sha256:7e0bacde1c660c0966dabcbb7ebc05ceee7e72f4dbe03aa2c6563e80f57925e0", "bytes": 49311, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12885-021-08412-4", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8236200", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE138080", "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=GSE138080", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE138080", "version": null, "note": "The raw data of the three microarray datasets (accession numbers GSE63514, GSE64217 and GSE138080) were downloaded from the GEO repository (https://www.ncbi.nlm.nih.gov/geo/). 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MCM2 is involved in the initiation of eukaryotic genome replication. It may be involved in the formation of replication forks and in the recruitment of other DNA replication-related proteins, and it regulates the helicase activity of the complex."], ["TOP2A", "DNA topoisomerase II a. These findings might provide target genes for the prognosis and treatment of cervical carcinoma. TOP2A controls and alters the topologic state of DNA during transcription. This nuclear enzyme is involved in processes such as chromosome condensation, chromatid separation, and the relief of torsional stress that occurs during DNA transcription and replication."], ["BLM", "BLM RecQ-like helicase. This Bloom-associated helicase unwinds a variety of DNA substrates including Holliday junctions and is involved in several pathways contributing to the maintenance of genome stability."], ["RMI2", "RecQ-mediated genome instability 2. RMI2 plays a role in homologous recombination-dependent DNA repair and is essential for genome stability."], ["EXO1", "Exonuclease 1. EXO1, with 5′ to 3′ exonuclease activity as well as RNase H activity, interacts with Msh2, which is involved in mismatch repair and recombination."], ["RFC4", "Replication factor C subunit 4. The elongation of primed DNA templates by DNA polymerase delta and DNA polymerase epsilon requires the accessory proteins proliferating cell nuclear antigen (PCNA) and replication factor C (RFC)."], ["PSCA", "Prostate stem cell antigen. PSCA is highly expressed in the prostate and also expressed in the bladder, placenta, colon, kidney, and stomach. This gene is upregulated in a large proportion of prostate cancers and is also detected in cancers of the bladder and pancreas."], ["KNTC1", "Kinetochore-associated 1. KNTC1 ensures proper chromosome segregation during cell division."], ["CDC45", "Cell division cycle 45. CDC45, an essential protein required for the initiation of DNA replication, is important for the early steps of DNA replication in eukaryotes."], ["GINS2", "GINS complex subunit 2. The GINS complex is essential for the initiation of DNA replication."], ["CXCL8", "C-X-C motif chemokine ligand 8. CXC is a major mediator of the inflammatory response. This protein is also secreted by tumor cells and promotes tumor migration, invasion, angiogenesis and metastasis. This chemokine is also a potent angiogenic factor."], ["TNFAIP6", "TNF alpha-induced protein 6. TNFAIP6 is a member of the hyaluronan-binding protein family. Its hyaluronan-binding domain is involved in extracellular matrix stability and cell migration. This protein is important in the protease network associated with inflammation."], ["CXCL5", "C-X-C motif chemokine ligand 5. Chemokines, which recruit and activate leukocytes, promote angiogenesis and remodel connective tissues. It plays a role in cancer cell proliferation, migration, and invasion."], ["CDA", "Cytidine deaminase. CDA is one of several deaminases responsible for maintaining the cellular pyrimidine pool."]], "row_count": 15, "column_count": 2, "numeric_cells": 11, "header_rows": 1, "locator": "section[15]/table-wrap[1]#Tab3"}}, {"id": "asset:table:pmid:34174849:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:feaba612f1c3de5112c99ab3aeb84e89c2581f8f4606b8b1ec542b0443248cff", "bytes": 755, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#Tab1", "version": null, "note": "KEGG pathway enrichment analysis of DEGs (DAVID)", "structure": {"pmcid": "PMC8236200", "section_index": 12, "section_title": "GO and KEGG pathway enrichment analyses", "row_count": 11, "column_count": 3}, "table": {"label": "Table 1", "caption": "KEGG pathway enrichment analysis of DEGs (DAVID)", "rows": [["Term", "Count", "P-value"], ["hsa04110: Cell cycle", "14", "7.05E-07"], ["hsa03030: DNA replication", "7", "5.88E-05"], ["hsa05323: Rheumatoid arthritis", "8", "0.001555896"], ["hsa04115: p53 signaling pathway", "7", "0.001840686"], ["hsa05219: Bladder cancer", "5", "0.007981073"], ["hsa04610: Complement and coagulation cascades", "6", "0.01080063"], ["hsa05146: Amoebiasis", "7", "0.017024795"], ["hsa04060: Cytokine-cytokine receptor interaction", "11", "0.019861501"], ["hsa04114: Oocyte meiosis", "7", "0.020898334"], ["hsa00590: Arachidonic acid metabolism", "5", "0.030571729"]], "row_count": 11, "column_count": 3, "numeric_cells": 30, "header_rows": 1, "locator": "section[12]/table-wrap[1]#Tab1"}}, {"id": "asset:table:pmid:34174849:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:d4185f1867a38264eaeb7505bd971d8a813236f43c1f145fb5ac6386abe3d3e8", "bytes": 1227, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[14]/table-wrap[1]#Tab2", "version": null, "note": "Discovering regions closely related to the PPI network (MCODE)", "structure": {"pmcid": "PMC8236200", "section_index": 14, "section_title": "PPI network construction and hub genes of cervical lesions", "row_count": 13, "column_count": 5}, "table": {"label": "Table 2", "caption": "Discovering regions closely related to the PPI network (MCODE)", "rows": [["Cluster", "Score (Density*#Nodes)", "Nodes", "Edges", "Genes"], ["1", "21.478", "24", "247", "TOP2A, KIF15, PRC1, SPAG5, KIF11, BIRC5, KIF23, MELK, DLGAP5, KIF2C, NUF2, MKI67, CENPE, NDC80, NEK2, AURKA, ASPM, CENPF, KIF20A, CDK1, TTK, CEP55, NUSAP1, KIF4A"], ["2", "16.625", "17", "133", "RPTN, SPRR1B, SPRR2E, SPRR2D, LCE3D, DSC2, SPRR2B, DSG1, PI3, TGM1, CSTA, IVL, LOR, FLG, SPRR3, SPRR1A, PPL"], ["3", "9.111", "10", "41", "CHEK1, MCM4, CDC45, MCM10, PRIM1, CDC7, CDT1, CDK2, POLE2, MCM8"], ["4", "8", "8", "28", "CRISP3, PRSS3, HP, LRG1, CSTB, TCN1, TNFAIP6, CDA"], ["5", "6", "6", "15", "SGOL2, CENPN, CASC5, CENPK, CDCA5, KNTC1"], ["6", "6", "6", "15", "KRT78, KRT2, KRT13, KRT1, KRT16, KRT4"], ["7", "6", "6", "15", "CXCR2, CXCR4, CXCL9, CXCL5, CXCL8, CXCL10"], ["8", "6", "6", "15", "LY6G6C, CEACAM7, PSCA, CEACAM5, LYPD3, LY6D"], ["9", "4", "4", "6", "RFC4, EXO1, TIPIN, RFC3"], ["10", "4", "4", "6", "PRSS3P2, SERPINB3, FABP5, S100A7"], ["11", "3.429", "8", "12", "DNA2, WDHD1, GINS2, DTL, RMI2, CDC6, BLM, MCM2"], ["12", "3", "3", "3", "ALOX12B, ALOX12, ALOX15B"]], "row_count": 13, "column_count": 5, "numeric_cells": 54, "header_rows": 1, "locator": "section[14]/table-wrap[1]#Tab2"}}, {"id": "asset:table:pmid:34174849:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:c8908234b26864f2fb5760c379dcdb1699ab37169d304875266022a30e3b61bf", "bytes": 3302, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[15]/table-wrap[1]#Tab3", "version": null, "note": "Functional analysis of possible prognostic genes for the progression of cervical cancer", "structure": {"pmcid": "PMC8236200", "section_index": 15, "section_title": "Expression and prognostic value of hub genes", "row_count": 15, "column_count": 2}, "table": {"label": "Table 3", "caption": "Functional analysis of possible prognostic genes for the progression of cervical cancer", "rows": [["Gene", "Function"], ["MCM2", "Minichromosome maintenance complex component 2. 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RMI2 plays a role in homologous recombination-dependent DNA repair and is essential for genome stability."], ["EXO1", "Exonuclease 1. EXO1, with 5′ to 3′ exonuclease activity as well as RNase H activity, interacts with Msh2, which is involved in mismatch repair and recombination."], ["RFC4", "Replication factor C subunit 4. The elongation of primed DNA templates by DNA polymerase delta and DNA polymerase epsilon requires the accessory proteins proliferating cell nuclear antigen (PCNA) and replication factor C (RFC)."], ["PSCA", "Prostate stem cell antigen. PSCA is highly expressed in the prostate and also expressed in the bladder, placenta, colon, kidney, and stomach. This gene is upregulated in a large proportion of prostate cancers and is also detected in cancers of the bladder and pancreas."], ["KNTC1", "Kinetochore-associated 1. KNTC1 ensures proper chromosome segregation during cell division."], ["CDC45", "Cell division cycle 45. CDC45, an essential protein required for the initiation of DNA replication, is important for the early steps of DNA replication in eukaryotes."], ["GINS2", "GINS complex subunit 2. The GINS complex is essential for the initiation of DNA replication."], ["CXCL8", "C-X-C motif chemokine ligand 8. CXC is a major mediator of the inflammatory response. This protein is also secreted by tumor cells and promotes tumor migration, invasion, angiogenesis and metastasis. This chemokine is also a potent angiogenic factor."], ["TNFAIP6", "TNF alpha-induced protein 6. TNFAIP6 is a member of the hyaluronan-binding protein family. Its hyaluronan-binding domain is involved in extracellular matrix stability and cell migration. This protein is important in the protease network associated with inflammation."], ["CXCL5", "C-X-C motif chemokine ligand 5. Chemokines, which recruit and activate leukocytes, promote angiogenesis and remodel connective tissues. 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