Integrative analysis of key candidate genes and signaling pathways in ovarian cancer by bioinformatics.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34253236", "kind": "science-record", "revision": 9, "content_hash": "sha256:803bd80d4da1ef71564a70c27cff901fac3778aa297d54cc0717fee618fbe6f5", "created_at": "2026-11-01T15:41:43Z", "updated_at": "2026-11-01T22:47:04Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Integrative analysis of key candidate genes and signaling pathways in ovarian cancer by bioinformatics.", "doi": "10.1186/s13048-021-00837-6", "pmid": "34253236", "authors": ["Cuicui Dong", "Xin Tian", "Fucheng He", "Jiayi Zhang", "Xiaojian Cui", "Qin He", "Ping Si", "Yongming Shen"], "journal": "Journal of ovarian research", "year": 2021, "abstract": "BACKGROUND: Ovarian cancer is one of the most common gynecological tumors, and among gynecological tumors, its incidence and mortality rates are fairly high. However, the pathogenesis of ovarian cancer is not clear. The present study aimed to investigate the differentially expressed genes and signaling pathways associated with ovarian cancer by bioinformatics analysis.\nMETHODS: The data from three mRNA expression profiling microarrays (GSE14407, GSE29450, and GSE54388) were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes between ovarian cancer tissues and normal tissues were identified using R software. The overlapping genes from the three GEO datasets were identified, and profound analysis was performed. The overlapping genes were used for pathway and Gene Ontology (GO) functional enrichment analysis using the Metascape online tool. Protein-protein interactions were analyzed with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). Subnetwork models were selected using the plugin molecular complex detection (MCODE) application in Cytoscape. Kaplan-Meier curves were used to analyze the univariate survival outcomes of the hub genes. The Human Protein Atlas (HPA) database and Gene Expression Profiling Interactive Analysis (GEPIA) were used to validate hub genes.\nRESULTS: In total, 708 overlapping genes were identified through analyses of the three microarray datasets (GSE14407, GSE29450, and GSE54388). These genes mainly participated in mitotic sister chromatid segregation, regulation of chromosome segregation and regulation of the cell cycle process. High CCNA2 expression was associated with poor overall survival (OS) and tumor stage. The expression of CDK1, CDC20, CCNB1, BUB1B, CCNA2, KIF11, CDCA8, KIF2C, NDC80 and TOP2A was increased in ovarian cancer tissues compared with normal tissues according to the Oncomine database. Higher expression levels of these seven candidate genes in ovarian cancer tissues compared with normal tissues were observed by GEPIA. The protein expression levels of CCNA2, CCNB1, CDC20, CDCA8, CDK1, KIF11 and TOP2A were high in ovarian cancer tissues, which was further confirmed via the HPA database.\nCONCLUSION: Taken together, our study provided evidence concerning the altered expression of genes in ovarian cancer tissues compared with normal tissues. In vivo and in vitro experiments are required to verify the results of the present study.", "claims": [{"id": "claim-method", "statement": "Three gene expression profiles (GSE54388, GSE14407, and GSE29450) were downloaded from the GEO database. GSE54388 contains 6 human ovarian surface epithelium samples and 16 tumor epithelial component samples. GSE14407 contains 12 healthy ovarian surface epithelium samples and 12 serous ovarian cancer epithelium samples. GSE29450 contains 10 ovarian cancer cell specimens and 10 normal ovarian surface epithelium specimens. The GSE54388, GSE14407, and GSE29450 data were all obtained with the Affymetrix Human Genome U133 Plus 2.0 Array platform. Expression data were normalized using median normalization [6]. DEGs between ovarian carcinoma tissues and normal tissues were obtained by using R statistical software and the limma Bioconductor package [7]. The criteria for DEG screening were FDR adjusted P < 0.05 and |logFC|≥ 1.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34253236", "locator": "sections[3] \"Differentially expressed genes analysis\" paragraph 2", "quote": "Three gene expression profiles (GSE54388, GSE14407, and GSE29450) were downloaded from the GEO database. GSE54388 contains 6 human ovarian surface epithelium samples and 16 tumor epithelial component samples. GSE14407 contains 12 healthy ovarian surface epithelium samples and 12 serous ovarian cancer epithelium samples. GSE29450 contains 10 ovarian cancer cell specimens and 10 normal ovarian surface epithelium specimens. The GSE54388, GSE14407, and GSE29450 data were all obtained with the Affymetrix Human Genome U133 Plus 2.0 Array platform. Expression data were normalized using median normalization [6]. DEGs between ovarian carcinoma tissues and normal tissues were obtained by using R statistical software and the limma Bioconductor package [7]. The criteria for DEG screening were FDR adjusted P < 0.05 and |logFC|≥ 1."}], "state": "complete"}, {"id": "claim-data-access", "statement": "GSE54388 contains 6 human ovarian surface epithelium samples and 16 tumor epithelial component samples.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34253236", "locator": "sections[3] \"Differentially expressed genes analysis\" paragraph 2", "quote": "GSE54388 contains 6 human ovarian surface epithelium samples and 16 tumor epithelial component samples."}], "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:34253236"], "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:GSE14407"], "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": {"fdr_threshold": "ith DEGs selected using FDR adjusted P < 0"}, "inputs": ["data:geo:GSE14407"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34253236", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": 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adjusted P < 0"}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Three gene expression profiles (GSE54388, GSE14407, and GSE29450) were downloaded from the GEO database. GSE54388 contains 6 human ovarian surface epithelium samples and 16 tumor epithelial component samples. GSE14407 contains 12 healthy ovarian surface epithelium samples and 12 serous ovarian cancer epithelium samples. GSE29450 contains 10 ovarian cancer cell specimens and 10 normal ovarian surface epithelium specimens. The GSE54388, GSE14407, and GSE29450 data were all obtained with the Affymetrix Human Genome U133 Plus 2.0 Array platform. Expression data were normalized using median normalization [6]. DEGs between ovarian carcinoma tissues and normal tissues were obtained by using R statistical software and the limma Bioconductor package [7]. The criteria for DEG screening were FDR adjusted P < 0.05 and |logFC|≥ 1."}}, {"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"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "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. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE54388", "GSE14407", "GSE29450"], "resolved_accessions": ["GSE54388", "GSE14407", "GSE29450"], "statements": ["GSE54388 contains 6 human ovarian surface epithelium samples and 16 tumor epithelial component samples."], "basis": "The paper names GSE54388, GSE14407, GSE29450 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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:34253236", "data:geo:GSE14407", "asset:table:pmid:34253236:1", "asset:table:pmid:34253236:2", "asset:table:pmid:34253236:3"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE14407"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:32:11Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 3, "usage": {"prompt_tokens": 21689, "completion_tokens": 1695, "cached_tokens": 784}}, "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:34253236", "type": "paper", "label": "pmid:34253236"}, {"id": "source:pmid:34253236", "type": "manuscript", "label": "PMID 34253236 full text"}, {"id": "data:geo:GSE14407", "type": "dataset", "label": "GEO GSE14407"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34253236", "type": "paper", "label": "pmid:34253236"}, {"id": "source:pmid:34253236", "type": "manuscript", "label": "PMID 34253236 full text"}, {"id": "data:geo:GSE14407", "type": "dataset", "label": "GEO GSE14407"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34253236", "type": "extraction", "used": ["source:pmid:34253236"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE14407", "type": "accession_resolution", "used": ["data:geo:GSE14407"], "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:34253236", "parent_hash": "sha256:f8fb46a217422efd38415312b38bae2d4c33418c5771222e6698de9e5dbd399d", "fork_of": null, "generation": 8}, "gaps": ["asset:data:geo:GSE14407 licence not read", "asset:data:geo:GSE14407 not downloaded", "asset:data:geo:GSE29450 licence not read", "asset:data:geo:GSE29450 not downloaded", "asset:data:geo:GSE54388 licence not read", "asset:data:geo:GSE54388 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ere identified through analyses of the three microarray datasets (GSE14407, GSE29450, and GSE54388)."], "order_basis": "paper_text_order:1489", "id": "assay:1"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["cancer tissues compared with normal tissues. In vivo and in vitro experiments are required to ver"], "order_basis": "paper_text_order:2437", "id": "assay:2"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Three gene expression profiles (GSE54388, GSE14407, and GSE29450) were downloaded from the GEO database. GSE54388 contains 6 human ovarian surface epithelium samples and 16 tumor epithelial component samples. GSE14407 contains 12 healthy ovarian surface epithelium samples and 12 serous ovarian cancer epithelium samples. GSE29450 contains 10 ovarian cancer cell specimens and 10 normal ovarian surface epithelium specimens. The GSE54388, GSE14407, and GSE29450 data were all obtained with the Affymetrix Human Genome U133 Plus 2.0 Array platform. Expression data were normalized using median normalization [6]. DEGs between ovarian carcinoma tissues and normal tissues were obtained by using R statistical software and the limma Bioconductor package [7]. The criteria for DEG screening were FDR adjusted P < 0.05 and |logFC|≥ 1."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}