Systemic Multi-Omics Analysis Reveals Amplified P4HA1 Gene Associated With Prognostic and Hypoxic Regulation in Breast Cancer.

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The molecular mechanisms underpinning hypoxia and their association with BC can contribute to a better understanding of tailored therapies. In this study, two hypoxic induced BC transcriptomic cohorts (GSE27813 and GSE47533) were assessed from the GEO database. The P4HA1 gene was identified as a putative candidate and significantly regulated in hypoxic BC cells compared to normal BC cells at different time intervals (6 h, 9 h, 16 h, 32 h, and 48 h). In patients with Luminal (p < 1E-12), triple-negative subclasses (p = 1.35059E-10), Stage 1 (p = 8.8817E-16), lymph node N1 (p = 1.62436E-12), and in the 40-80 age group (p = 1.62447E-12), the expression of P4HA1 was closely associated with the clinical subtypes of BC. Furthermore, at the 10q22.1 chromosomal band, the P4HA1 gene displayed a high copy number elevation and was associated with a poor clinical regimen with overall survival, relapse-free survival, and distant metastases-free survival in BC patients. In addition, using BioGRID, the protein-protein interaction (PPI) network was built and the cellular metabolic processes, and hedgehog pathways are functionally enriched with GO and KEGG terms. This tentative result provides insight into the molecular function of the P4HA1 gene, which is likely to promote hypoxic-mediated carcinogenesis, which may favor early detection of BC and therapeutic stratification.", "claims": [{"id": "claim-method", "statement": "The Cox proportional hazard regression model with microarray cohort GSE22133 was examined to verify the patient’s overall survival between the expression of the P4HA1 gene and the BC’s clinical characteristics.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33692831", "locator": "sections[7] \"Clinical Regimen Prognosis\" paragraph 2", "quote": "The Cox proportional hazard regression model with microarray cohort GSE22133 was examined to verify the patient’s overall survival between the expression of the P4HA1 gene and the BC’s clinical characteristics."}], "state": "complete"}, {"id": "claim-data-access", "statement": "This study was carried out on publicly available data on Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/) with accession numbers: GSE27813, GSE47533, and GSE22133.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33692831", "locator": "sections[20] \"Data Availability Statement\" paragraph 2", "quote": "This study was carried out on publicly available data on Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/) with accession numbers: GSE27813, GSE47533, and GSE22133."}], "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:33692831"], "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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