Expression Profiles Reveal Involvement of VEGF, IGF1, BIRC5, and MMP1 in Vulvar Carcinogenesis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33888009", "kind": "science-record", "revision": 7, "content_hash": "sha256:7e943d28ef7cf564b06ec296739b938a930ca17f918083ce85eacecb17ed2d5b", "created_at": "2026-11-01T15:41:33Z", "updated_at": "2026-11-01T21:25:12Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Expression Profiles Reveal Involvement of VEGF, IGF1, BIRC5, and MMP1 in Vulvar Carcinogenesis.", "doi": "10.1177/15330338211004922", "pmid": "33888009", "authors": ["Tao Zhang", "Qin Liu", "Minghua Yu", "Yibing Lan", "Jianghong Zhou"], "journal": "Technology in cancer research & treatment", "year": 2021, "abstract": "OBJECTIVE: The objective of this study was to identify key genes and shed light on the underlying molecular mechanisms of vulvar squamous cell carcinoma (VSCC).\nMETHODS: Bioinformatic software was utilized for the identification and characterization of key differentially expressed genes (DEGs) from microarrays GSE63678 and GSE38228, which contain VSCC and normal vulvar tissue data. These microarrays were obtained from Gene Expression Omnibus (GEO). Immunohistochemical assays (55 VSCC and 50 normal vulvar tissues) were utilized to validate the expression of VEGF, IGF1, BIRC5, and MMP1 screened from the identified DEGs. SPSS 18.0 software was used for statistical analyses of the relationships between IGF1, BIRC5, VEGF, MMP1 expression levels and patient clinicopathological characteristics.\nRESULTS: A total of 141 DEGs were identified, among which 18 genes were closely correlated with the biological characteristics of VSCC. Four of the 18 genes (VEGF, IGF1, BIRC5, and MMP1) screened from the GEO database were markedly enriched in pathways in cancer (P < 0.05), and could be considered key genes in VSCC based on KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis in DAVID (Database for Annotation, Visualization and Integrated Discovery).The expression levels of these 4 hub genes, determined by immunohistochemical assays, were consistent with the bioinformatics results. Higher expression of IGF1 showed significant association with well-differentiated carcinomas (P = 0.017).BIRC5 expression levels showed a positive correlation with clinical stage (P = 0.039); compared with those in menopause for over 10 years, patients in menopause for less than 10 years at the time of diagnosis tended to have significantly higher expression of BIRC5 (P = 0.003). VEGF and MMP1 expression levels were not correlated with any of the tested clinicopathological characteristics.\nCONCLUSION: VEGF, IGF1, BIRC5, and MMP1 were identified as being associated with VSCC using integrated bioinformatic methods, which may provide important insights into the pathogenesis of this disease and help to identify new biomarkers.", "claims": [{"id": "claim-method", "statement": "DEGs between the 2 groups were identified by using the GEO2R online tool8 with statistical significance reached at |logFC| > 1 and adjusted P value < 0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33888009", "locator": "sections[4] \"Identification of DEGs\" paragraph 2", "quote": "DEGs between the 2 groups were identified by using the GEO2R online tool8 with statistical significance reached at |logFC| > 1 and adjusted P value < 0.05."}], "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:33888009"], "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:GSE38228"], "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:GSE38228"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33888009", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1177/15330338211004922", "sha256": "sha256:a1d99994da3d143b1235af92740fea6a8e30c1ef6663fc63b24a7b48a5729ec6", "bytes": 26527, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1177/15330338211004922", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8071978", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE38228", "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=GSE38228", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE38228", "version": null, "note": "Microarray data of GSE63678 comprise 6 VSCC tumor and 13 normal vulvar tissue samples, while the GSE38228 profile consists of 7 VSCC tumor and 5 normal vulvar tissues samples. The VSCC-associated gene expression datasets GSE63678 and GSE38228 were downloaded from Gene Expression Omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Microarray data of GSE63678 comprise 6 VSCC tumor and 13 normal vulvar tissue samples, while the GSE38228 profile consists of 7 VSCC tumor and 5 normal vulvar tissues samples. The VSCC-associated gene expression datasets GSE63678 and GSE38228 were downloaded from Gene Expression Omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo/).", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM937042", "GSM937043", "GSM937044", "GSM937045", "GSM937046", "GSM937047", "GSM937048", "GSM937049", "GSM937050", "GSM937051", "GSM937052", "GSM937053", "GSM937054", "GSM937055", "GSM937056", "GSM937057", "GSM937058", "GSM937059"], "sample_count": 18, "group_sizes": null, "group_sizes_basis": null, "platform": "10558", "taxon": "Homo sapiens", "title": "Expression analysis of 13 squamous cell carcinomas arising in the vulva", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE63678", "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=GSE63678", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE63678", "version": null, "note": "Microarray data of GSE63678 comprise 6 VSCC tumor and 13 normal vulvar tissue samples, while the GSE38228 profile consists of 7 VSCC tumor and 5 normal vulvar tissues samples. The VSCC-associated gene expression datasets GSE63678 and GSE38228 were downloaded from Gene Expression Omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Microarray data of GSE63678 comprise 6 VSCC tumor and 13 normal vulvar tissue samples, while the GSE38228 profile consists of 7 VSCC tumor and 5 normal vulvar tissues samples. The VSCC-associated gene expression datasets GSE63678 and GSE38228 were downloaded from Gene Expression Omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo/).", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM1555075", "GSM1555076", "GSM1555077", "GSM1555078", "GSM1555079", "GSM1555080", "GSM1555081", "GSM1555082", "GSM1555083", "GSM1555084", "GSM1555085", "GSM1555086", "GSM1555087", "GSM1555088", "GSM1555089", "GSM1555090", "GSM1555091", "GSM1555092", "GSM1555093", "GSM1555094", "GSM1555095", "GSM1555096", "GSM1555097", "GSM1555098", "GSM1555099", "GSM1555100", "GSM1555101", "GSM1555102", "GSM1555103", "GSM1555104", "GSM1555105", "GSM1555106", "GSM1555107", "GSM1555108", "GSM1555109"], "sample_count": 35, "group_sizes": null, "group_sizes_basis": null, "platform": "571", "taxon": "Homo sapiens", "title": "Expression data from Vulvar, Cervical, Endometrial Carcinoma 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": "asset:table:pmid:33888009:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:b68db7bf44393e5b080344ed015404465a554e773685f6058dc3d9b934be0d48", "bytes": 359, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[1]#table1-15330338211004922", "version": null, "note": "Entire 141 Common DEGs Were Identified From 2 Profile Datasets, Including 39 Up-Regulated Genes and 102 Down-Regulated Genes in the Vulvar Cancer Tissues Compared to Normal Vulvar Tissues.", "structure": {"pmcid": "PMC8071978", "section_index": 10, "section_title": "Identification of DEGs in VSCC", "row_count": 0, "column_count": 0}, "table": {"label": "Table 1.", "caption": "Entire 141 Common DEGs Were Identified From 2 Profile Datasets, Including 39 Up-Regulated Genes and 102 Down-Regulated Genes in the Vulvar Cancer Tissues Compared to Normal Vulvar Tissues.", "rows": [], "row_count": 0, "column_count": 0, "numeric_cells": 0, "header_rows": 0, "locator": "section[10]/table-wrap[1]#table1-15330338211004922"}}, {"id": "asset:table:pmid:33888009:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:f7f48658c7fd9a6d42a1bcb090423251ce589c59a6b177fb32566f721a64341a", "bytes": 218, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#table2-15330338211004922", "version": null, "note": "KEGG Pathway Analysis of 18 Core Genes in VSCC.", "structure": {"pmcid": "PMC8071978", "section_index": 12, "section_title": "Analysis of 18 Core Genes for KEGG Pathway Enrichment", "row_count": 0, "column_count": 0}, "table": {"label": "Table 2.", "caption": "KEGG Pathway Analysis of 18 Core Genes in VSCC.", "rows": [], "row_count": 0, "column_count": 0, "numeric_cells": 0, "header_rows": 0, "locator": "section[12]/table-wrap[1]#table2-15330338211004922"}}, {"id": "asset:table:pmid:33888009:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:aaf4712154f48e089538651f6caeeef350a1bac2b4009d0e164ada9720fcb8e4", "bytes": 218, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#table3-15330338211004922", "version": null, "note": "Protein Expression in Different Vulvar Tissue.a", "structure": {"pmcid": "PMC8071978", "section_index": 13, "section_title": "Validation of VEGF, IGF1, BIRC5, and MMP1 Expression With Immunohistochemical Assay in Normal Vulvar Tissues Versus Vulvar Cancer Samples", "row_count": 0, "column_count": 0}, "table": {"label": "Table 3.", "caption": "Protein Expression in Different Vulvar Tissue.a", "rows": [], "row_count": 0, "column_count": 0, "numeric_cells": 0, "header_rows": 0, "locator": "section[13]/table-wrap[1]#table3-15330338211004922"}}, {"id": "asset:table:pmid:33888009:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:6c6f11469bd54e768ce18f794cc6b93edad562e739bfeb2c87c04f9f122c3a3a", "bytes": 278, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[14]/table-wrap[1]#table4-15330338211004922", "version": null, "note": "Association Between the Expression of IGF1, BIRC5, VEGF, and MMP1 and Clinicopathological Characteristics.a", "structure": {"pmcid": "PMC8071978", "section_index": 14, "section_title": "Relationships Between IGF1, BIRC5, VEGF, MMP1 Expression Levels and Patients’ Clinicopathological Characteristics", "row_count": 0, "column_count": 0}, "table": {"label": "Table 4.", "caption": "Association Between the Expression of IGF1, BIRC5, VEGF, and MMP1 and Clinicopathological Characteristics.a", "rows": [], "row_count": 0, "column_count": 0, "numeric_cells": 0, "header_rows": 0, "locator": "section[14]/table-wrap[1]#table4-15330338211004922"}}], "gaps": ["asset:data:geo:GSE38228 not downloaded", "asset:data:geo:GSE38228 licence not read", "asset:data:geo:GSE63678 not downloaded", "asset:data:geo:GSE63678 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "Pathway Enrichment"}}, {"id": "method-2", "family": null, "specific": null, "label": "GEO2R online tool", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "DEGs between the 2 groups were identified by using the GEO2R online tool8 with statistical significance reached at |logFC| > 1 and adjusted P value < 0.05."}}], "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", "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": ["pathway_enrich"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: pathway_enrichment."}, "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": ["GSE63678", "GSE38228"], "resolved_accessions": ["GSE63678", "GSE38228"], "statements": ["Microarray data of GSE63678 comprise 6 VSCC tumor and 13 normal vulvar tissue samples, while the GSE38228 profile consists of 7 VSCC tumor and 5 normal vulvar tissues samples. The VSCC-associated gene expression datasets GSE63678 and GSE38228 were downloaded from Gene Expression Omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo/)."], "basis": "The paper names GSE63678, GSE38228 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["pathway_enrich"], "assets": ["source:pmid:33888009", "data:geo:GSE38228", "asset:table:pmid:33888009:1", "asset:table:pmid:33888009:2", "asset:table:pmid:33888009:3", "asset:table:pmid:33888009:4"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE38228"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:29:22Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 3, "usage": {"prompt_tokens": 20049, "completion_tokens": 1848, "cached_tokens": 12800}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:33888009", "type": "paper", "label": "pmid:33888009"}, {"id": "source:pmid:33888009", "type": "manuscript", "label": "PMID 33888009 full text"}, {"id": "data:geo:GSE38228", "type": "dataset", "label": "GEO GSE38228"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33888009", "type": "paper", "label": "pmid:33888009"}, {"id": "source:pmid:33888009", "type": "manuscript", "label": "PMID 33888009 full text"}, {"id": "data:geo:GSE38228", "type": "dataset", "label": "GEO GSE38228"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33888009", "type": "extraction", "used": ["source:pmid:33888009"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE38228", "type": "accession_resolution", "used": ["data:geo:GSE38228"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:33888009", "parent_hash": "sha256:f0bdc7965838175c70ca13053a07b96270935639ee3d0d8addeb45488caff31d", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE38228 licence not read", "asset:data:geo:GSE38228 not downloaded", "asset:data:geo:GSE63678 licence not read", "asset:data:geo:GSE63678 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["obtained from Gene Expression Omnibus (GEO). Immunohistochemical assays (55 VSCC and 50 normal vulvar tissues", "n levels of these 4 hub genes, determined by immunohistochemical assays, were consistent with the bioinformat", "VEGF, IGF1, BIRC5, and MMP1 Expression With Immunohistochemical Assay in Normal Vulvar Tissues Versus Vulvar", "lidation of VEGF, IGF1, BIRC5, and MMP1 with immunohistochemical assay of normal vulvar tissues versus vulvar"], "order_basis": "paper_text_order:504", "id": "assay:1"}, {"role": "analysis", "definition_id": "network_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["pathway_enrich"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Pathway Enrichment"], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}