Expression changes in pelvic organ prolapse: a systematic review and in silico study.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:28794464", "kind": "science-record", "revision": 9, "content_hash": "sha256:4d37d93d3e2c316d5c09703850120dd4bf02b08bceb919efa9e1c3650749bc28", "created_at": "2026-11-01T15:40:27Z", "updated_at": "2026-11-01T22:43:04Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Expression changes in pelvic organ prolapse: a systematic review and in silico study.", "doi": "10.1038/s41598-017-08185-6", "pmid": "28794464", "authors": ["Maryam B Khadzhieva", "Dmitry S Kolobkov", "Svetlana V Kamoeva", "Lyubov E Salnikova"], "journal": "Scientific reports", "year": 2017, "abstract": "Pelvic organ prolapse (POP) is a highly disabling condition common for a vast number of women worldwide. To contribute to existing knowledge in POP pathogenesis, we performed a systematic review of expression studies on both specific gene and whole-genome/proteome levels and an in silico analysis of publicly available datasets related to POP development. The most extensively investigated genes in individual studies were related to extracellular matrix (ECM) organization. Three premenopausal and two postmenopausal sets from two Gene Expression Omnibus (GEO) studies (GSE53868 and GSE12852) were analyzed; Gene Ontology (GO) terms related to tissue repair (locomotion, biological adhesion, immune processes and other) were enriched in all five datasets. Co-expression was higher in cases than in controls in three premenopausal sets. The shared between two or more datasets up-regulated genes were enriched with those related to inflammatory bowel disease (IBD) in the NHGRI GWAS Catalog. ECM-related genes were not over-represented among differently expressed genes. Up-regulation of genes related to tissue renewal probably reflects compensatory mechanisms aimed at repair of damaged tissue. Inefficiency of this process may have different origins including age-related deregulation of gene expression.", "claims": [{"id": "claim-method", "statement": "Results of two studies submitted to the repository Gene Expression Omnibus (GEO) were processed with GEO2R – an interactive web tool which exploits Limma R packages from Bioconductor project17 for comparison of user-defined groups of samples under the same experimental conditions (http://www.ncbi.nlm.nih.gov/geo/geo2r/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:28794464", "locator": "sections[13] \"Microarray data processing\" paragraph 2", "quote": "Results of two studies submitted to the repository Gene Expression Omnibus (GEO) were processed with GEO2R – an interactive web tool which exploits Limma R packages from Bioconductor project17 for comparison of user-defined groups of samples under the same experimental conditions (http://www.ncbi.nlm.nih.gov/geo/geo2r/)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Three premenopausal and two postmenopausal sets from two Gene Expression Omnibus (GEO) studies (GSE53868 and GSE12852) were analyzed;", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:28794464", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Three premenopausal and two postmenopausal sets from two Gene Expression Omnibus (GEO) studies (GSE53868 and GSE12852) were analyzed;"}], "state": "complete"}, {"id": "claim-target-result", "statement": "The paper combined a systematic review with in silico analysis of two public GEO studies, GSE53868 and GSE12852; GEO2R with Limma was used for microarray comparisons, and KOBAS 3.0 with REVIGO was used for gene-set enrichment analysis and GO-term summarization. No numerical result was reported specifically for this methodological target.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:28794464", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "To contribute to existing knowledge in POP pathogenesis, we performed a systematic review of expression studies on both specific gene and whole-genome/proteome levels and an in silico analysis of publicly available datasets related to POP development."}, {"asset": "source:pmid:28794464", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Three premenopausal and two postmenopausal sets from two Gene Expression Omnibus (GEO) studies (GSE53868 and GSE12852) were analyzed; Gene Ontology (GO) terms related to tissue repair (locomotion, biological adhesion, immune processes and other) were enriched in all five datasets."}, {"asset": "source:pmid:28794464", "locator": "sections[13] \"Microarray data processing\" paragraph 2", "quote": "Results of two studies submitted to the repository Gene Expression Omnibus (GEO) were processed with GEO2R – an interactive web tool which exploits Limma R packages from Bioconductor project17 for comparison of user-defined groups of samples under the same experimental conditions (http://www.ncbi.nlm.nih.gov/geo/geo2r/)."}, {"asset": "source:pmid:28794464", "locator": "sections[14] \"Gene set enrichment analysis\" paragraph 2", "quote": "These gene sets were treated with KOBAS 3.0 resource7 for Gene Ontology (GO) enrichment analysis."}, {"asset": "source:pmid:28794464", "locator": "sections[14] \"Gene set enrichment analysis\" paragraph 2", "quote": "Web server REVIGO was utilized for summarizing GO terms, which was guided by the P-value9."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The paper combined a systematic review with in silico analysis of two public GEO studies, GSE53868 and GSE12852; GEO2R with Limma was used for microarray comparisons, and KOBAS 3.0 with REVIGO was used for gene-set enrichment analysis and GO-term summarization. No numerical result was reported specifically for this methodological target.", "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:28794464"], "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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5 controls (45.5 ± 11.4)", "Microarray gene expression", "Down-regulation in POP patients: FC > 2.0, 257 genes; FC > 5, 20 genes; FC > 10, 3 genes. Up-regulation in POP patients: FC > 2.0, 479 genes; FC > 5, 18 genes; FC > 10, 2 genes.", "The genes MYBPH (FC 24.7), MYH3 (FC 17.4) and COMP (FC 6.0) were down-regulated, while smooth muscle myosin heavy chain (FC 11.8), MLCK (FC 5.77) and TNC (FC 5.1) genes were up-regulated in POP patients in comparison with controls.", "No", "10"], ["Full-thickness vaginal wall biopsies from patients with POP and age-, parity -, and body mass index -matched controlsb", "5 PrM cases, 5 PrM controls", "Microarray gene expression", "Upregulated genes (n = 50) comprised those involved in smooth muscle contraction, proteolysis, response to oxidative stress, transcriptional regulation, cytoskeletal organization, and lipid catabolism.", "The PPP1R12A and ADAMTS1 genes were up-regulated 2.4 and 4-fold in cases compared to controls.", "mRNA analysis for 4 matched pairs of POP/control tissues", "12"], ["USLs and RLs from mixed ethnicity patients with uterine prolapse (POP-Q stage ≥ 2) and controls", "8 POP patients (5 PrM and 3 PM); 9 controls (6 PrM and 3 PM)", "Microarray gene expression", "In a combined analysis of expression changes in USLs and RLs, 1521 genes were up-regulated and 1193 genes were down-regulated with FC change 1.5. 249 up-regulated gene probes met FDR criteria ≤ 5.18.", "After FDR correction for multiple testing, genes enriched for ‘immunity and defense’ were up-regulated in POP patients.", "qRT-PCR Up-regulation in POP patients: IL-6 (FC 9.8), ATF3 (FC 2.6), THBS1 (FC 3.5) and PTGS2 (FC 2.4)", "13"], ["Pubocervical fascia from females with POP and SUI and from asymptomatic controlsb", "4 cases (PM); 3 controls (PM)", "Proteomic analysis (two-dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry)", "7 proteins with an expression FC more than two (3.8 ─ 54.3-fold).", "The expression levels of transgelin (FC 54.3), smooth muscle gamma-actin (FC 6.3), myosin light polypeptide 6 (FC 4.4), and alpha-1 antitrypsin precursor (FC 4.3) were higher in patients than in controls.", "2-DE western blot analysis for transgelin", "11"], ["USLs from Asian women with POP-Q stage 3-4 (cases) or 0-1 (controls)", "12 cases (PM), 5 controls (PM)", "Microarray gene expression", "143 genes were up-regulated and 87 genes were down-regulated with FC > 1.5 (P < 0.05).", "The expression levels of ESRRA (FC 0.434) decreased, while the expression levels of DAPK2 (FC 2.013), IL15 (FC 2.1) and STAP2 (FC 2.392) increased in POP patients compared with controls.", "qRT-PCR for the genes ESRRA, DAPK2, IL15, STAP2", "14"], ["USLs from patients with uterine prolapse and controlsb", "16 POP patients (15 patients PM); 9 controls (7 females PM)", "Microarray gene expression", "21 up-regulated and 7 down-regulated genes with FC > 2.0 were found in patients with POP compared to the control group.", "Down-regulation in POP patients compared with controls after FDR correction for multiple testing: NKX2-3 (FC 2.6) in the whole set; KIF11 (FC 1.3) in patients with ≥ 3 deliveries compared to patients with < 3 deliveries; UGT1A1 (FC 1.4), SCARB1 (FC 3.2) and NKX2-3 (FC 6.2) in PrM patients compared to PrM controls; UGT1A1 (FC 1.1) in PM patients compared to PM controls.", "No", "15"], ["USL samples of patients with stage II to stage IV POP (mean age 61 years) and normal controls (mean age 55 years)b", "No data", "RNA-seq (a HiSeqTM 2500 platform (Illumina))", "After FDR-correction, a total of 81 genes had different expression patterns in POP patients and controls. Sixty-six DEGs did not differ between the POP samples with different stages", "Canonical Wnt receptor signaling pathway was the most significantly enriched GO term (P- value = 3.33E-07), and neuroactive ligand-receptor interaction was the most significantly enriched pathway (P- value = 1.24E-03).", "No", "16"]], "row_count": 8, "column_count": 7, "numeric_cells": 34, "header_rows": 1, "locator": "section[4]/table-wrap[1]#Tab1"}}, {"id": "asset:table:pmid:28794464:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:71e3f09f8eb7be849725e011a58681f7171648345caa0c967677c35b6b7b3f55", "bytes": 1220, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[5]/table-wrap[1]#Tab2", "version": null, "note": "Characteristics of the POP datasets in the Gene Expression Omnibus (GEO) database repository.", "structure": {"pmcid": "PMC5550478", "section_index": 5, "section_title": "Overview of available GEO datasets for POP", "row_count": 10, "column_count": 7}, "table": {"label": "Table 2", "caption": "Characteristics of the POP datasets in the Gene Expression Omnibus (GEO) database repository.", "rows": [["Dataset", "Reference", "Tissue", "Number of samples", "GEO accession no; Platform", "Number of DEGa with FDR-corrected P - value < 0.05", "Number of DEGa with FC ≥ 2.0 and P - value < 0.05 (uncorrected for multiplicity)"], ["PrM Caucasian women (cystocele POP-Q stage ≥ 2), n = 12", "Citation missing", "AVW (POP site) versus precervical AVW (non POP site)", "12 women (24 samples)", "GSE53868; GPL18142 Agilent-014850 WHGM 4 × 44K G4112F", "50 (↑ 31; ↓ 19)", "74 (↑ 58; ↓16)"], ["PrM POP women, n = 5b", "Brizzolara et al.13", "RLs", "5", "GSE12852; GPL2986 ABI Human Genome Survey Microarray Version 2", "PrM_RLs set 0", "PrM_RLs set 287 (↑ 246; ↓ 41)"], ["USLs", "5"], ["PrM controls, n = 6b", "RLs", "6", "PrM_USLs set 0", "PrM_USLs set 972 (↑ 949; ↓23)"], ["USL", "6"], ["PM POP women, n = 3b", "RL", "3", "PM_RLs set 0", "PM_RLs set 485 (↑ 345; ↓ 140)"], ["USL", "3"], ["PM controls, n = 3b", "RL", "3", "PM_USLs set 2 (↑ 2; ↓ 0)", "PM_USLs set 494(↑ 263; ↓ 231)"], ["USL", "3"]], "row_count": 10, "column_count": 7, "numeric_cells": 29, "header_rows": 1, "locator": "section[5]/table-wrap[1]#Tab2"}}, {"id": "asset:table:pmid:28794464:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:79797698d2e0a2d8d38f62d4cfbc5ce2c116241beb93e1e810450ef79f26eb53", "bytes": 2134, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[8]/table-wrap[1]#Tab3", "version": null, "note": "The results of gene set enrichment analysis for shared genes up-regulated in POP tissues.", "structure": {"pmcid": "PMC5550478", "section_index": 8, "section_title": "Enrichment analysis (GO, KEGG, GWAS Catalog) for the shared gene set", "row_count": 19, "column_count": 6}, "table": {"label": "Table 3", "caption": "The results of gene set enrichment analysis for shared genes up-regulated in POP tissues.", "rows": [["Term", "Input number", "Background number", "P - value", "Corrected P - value", "Genes"], ["KEGG Pathway"], ["Malaria (hsa05144)", "7", "49", "1,25E-09", "1,93E-07", "COMP, ICAM1, IL6, CXCL8, CCL2, THBS1, THBS4"], ["Influenza A (hsa05164)", "8", "176", "3,48E-07", "2,69E-05", "NLRP3, ICAM1, IL6, CXCL8, NXF3, CCL2, SOCS3, RSAD2"], ["Rheumatoid arthritis (hsa05323)", "5", "91", "2,51E-05", "1,19E-03", "CTSK, ICAM1, IL6, CXCL8, CCL2"], ["PI3K-Akt signaling pathway (hsa04151)", "8", "342", "3,91E-05", "1,19E-03", "CDKN1A, COMP, GNGT1, IL6, MCL1, PPP2R2C, THBS1, THBS4"], ["AGE-RAGE signaling pathway in diabetic complications (hsa04933)", "5", "101", "4,04E-05", "1,19E-03", "ICAM1, IL6, CXCL8, SERPINE1, CCL2"], ["Chagas disease (American trypanosomiasis)", "5", "104", "4,62E-05", "1,19E-03", "IL6, CXCL8, SERPINE1, PPP2R2C, CCL2"], ["Hepatitis C (hsa05142)", "5", "133", "1,41E-04", "2,43E-03", "CDKN1A, CXCL8, LDLR, PPP2R2C, SOCS3"], ["Hepatitis B (hsa05161)", "5", "146", "2,15E-04", "3,32E-03", "CDKN1A, EGR2, EGR3, IL6, CXCL8"], ["Phagosome (hsa04145)", "5", "155", "2,80E-04", "3,95E-03", "COMP, FCAR, THBS1, THBS4, COLEC11"], ["HTLV-I infection (hsa05166)", "6", "259", "3,90E-04", "4,91E-03", "CDKN1A, EGR2, ICAM1, IL6, ATF3, IL1R2"], ["Transcriptional misregulation in cancer (hsa05202)", "5", "180", "5,44E-04", "5,63E-03", "CDKN1A, IL6, CXCL8, IL1R2, NR4A3"], ["Herpes simplex infection (hsa05168)", "5", "186", "6,29E-04", "6,09E-03", "IL6, NXF3, CCL2, TNFSF14, SOCS3"], ["Cytokine-cytokine receptor interaction (hsa04060)", "5", "265", "2,89E-03", "2,03E-02", "IL6, CXCL8, CCL2, IL1R2, TNFSF14"], ["Pathways in cancer (hsa05200)", "6", "397", "3,31E-03", "2,13E-02", "CDKN1A, CKS2, GNGT1, IL6, CXCL8, BDKRB1"], ["The NHGRI GWAS Catalog"], ["Inflammatory bowel disease", "9", "271", "8,03E-07", "1,26E-04", "BORCS5, CCL2, CXCL8, ICAM1, IL1R2, NFIL3, PTPRC, SLC11A1, SLC22A4"], ["Crohn’s disease", "6", "256", "3,68E-04", "1,15E-02", "SLC22A4, ICAM1, CCL2, TAGAP, PTPRC, CNNM1"]], "row_count": 19, "column_count": 6, "numeric_cells": 82, "header_rows": 1, "locator": "section[8]/table-wrap[1]#Tab3"}}], "gaps": ["asset:data:geo:GSE12852 not downloaded", "asset:data:geo:GSE12852 licence not read", "asset:data:geo:GSE53868 not downloaded", "asset:data:geo:GSE53868 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "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": 1.0, "band": "verbatim", "quote": "Results of two studies submitted to the repository Gene Expression Omnibus (GEO) were processed with GEO2R – an interactive web tool which exploits Limma R packages from Bioconductor project17 for comparison of user-defined groups of samples under the same experimental conditions (http://www.ncbi.nlm.nih.gov/geo/geo2r/)."}}, {"id": "method-2", "family": "genetic_association", "specific": "gwas", "label": "Genetic association (GWAS / linkage / MR)", "dsl_operations": ["gwas_locus_scan"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["genotype_phenotype_table"], "evidence": {"score": 0.7, "band": "medium", "quote": "GWAS"}}], "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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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