Endocrine Disrupting Chemicals Influence Hub Genes Associated with Aggressive Prostate Cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36834602", "kind": "science-record", "revision": 4, "content_hash": "sha256:3a6b64d1c5213dea17cadc402d08d40fdda1da28155c66e7a62b68c05ec47f72", "created_at": "2026-11-01T19:01:27Z", "updated_at": "2026-11-01T22:51:21Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Endocrine Disrupting Chemicals Influence Hub Genes Associated with Aggressive Prostate Cancer.", "doi": "10.3390/ijms24043191", "pmid": "36834602", "authors": ["Diaaidden Alwadi", "Quentin Felty", "Changwon Yoo", "Deodutta Roy", "Alok Deoraj"], "journal": "International journal of molecular sciences", "year": 2023, "abstract": "Prostate cancer (PCa) is one of the most frequently diagnosed cancers among men in the world. Its prevention has been limited because of an incomplete understanding of how environmental exposures to chemicals contribute to the molecular pathogenesis of aggressive PCa. Environmental exposures to endocrine-disrupting chemicals (EDCs) may mimic hormones involved in PCa development. This research aims to identify EDCs associated with PCa hub genes and/or transcription factors (TF) of these hub genes in addition to their protein-protein interaction (PPI) network. We are expanding upon the scope of our previous work, using six PCa microarray datasets, namely, GSE46602, GSE38241, GSE69223, GSE32571, GSE55945, and GSE26126, from the NCBI/GEO, to select differentially expressed genes based on |log2FC| (fold change) ≥ 1 and an adjusted p-value < 0.05. An integrated bioinformatics analysis was used for enrichment analysis (using DAVID.6.8, GO, KEGG, STRING, MCODE, CytoHubba, and GeneMANIA). Next, we validated the association of these PCa hub genes in RNA-seq PCa cases and controls from TCGA. The influence of environmental chemical exposures, including EDCs, was extrapolated using the chemical toxicogenomic database (CTD). A total of 369 overlapping DEGs were identified associated with biological processes, such as cancer pathways, cell division, response to estradiol, peptide hormone processing, and the p53 signaling pathway. Enrichment analysis revealed five up-regulated (NCAPG, MKI67, TPX2, CCNA2, CCNB1) and seven down-regulated (CDK1, CCNB2, AURKA, UBE2C, BUB1B, CENPF, RRM2) hub gene expressions. Expression levels of these hub genes were significant in PCa tissues with high Gleason scores ≥ 7. These identified hub genes influenced disease-free survival and overall survival of patients 60-80 years of age. The CTD studies showed 17 recognized EDCs that affect TFs (NFY, CETS1P54, OLF1, SRF, COMP1) that are known to bind to our PCa hub genes, namely, NCAPG, MKI67, CCNA2, CDK1, UBE2C, and CENPF. These validated differentially expressed hub genes can be potentially developed as molecular biomarkers with a systems perspective for risk assessment of a wide-ranging list of EDCs that may play overlapping and important role(s) in the prognosis of aggressive PCa.", "claims": [{"id": "claim-method", "statement": "GEPIA2 uses the log-rank test, at the Mantel–Cox test (Cox regression analysis), for the hypothesis test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36834602", "locator": "sections[17] \"4.7. Survival Analysis with Hub Genes\" paragraph 3", "quote": "GEPIA2 uses the log-rank test, at the Mantel–Cox test (Cox regression analysis), for the hypothesis test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated during the current study are available from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36834602", "locator": "sections[27] \"notes\" paragraph 1", "quote": "The datasets generated during the current study are available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "These identified hub genes influenced disease-free survival and overall survival of patients 60–80 years of age.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36834602", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "These identified hub genes influenced disease-free survival and overall survival of patients 60–80 years of age."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "These identified hub genes influenced disease-free survival and overall survival of patients 60–80 years of age.", "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:36834602"], "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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GEO2R is a tool that permits resea", "d to find the overlapping DEGs among the six microarray datasets. Volcano plots were used to indicat"], "order_basis": "paper_text_order:683", "id": "assay:1"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ed the association of these PCa hub genes in RNA-seq PCa cases and controls from TCGA. The influe", "with/without TP53 mutation were matched with RNA-seq data. 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