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pmid:38795391
Defining three ferroptosis-based molecular subtypes and developing a prognostic risk model for high-grade serous ovarian cancer.
Xiang Sun · Wenbin He · Baohua Lin · Weiming Huang · Danping Ye
Aging · 2024 doi:10.18632/aging.205857
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Experiment
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Complete file
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However, its underlying mechanism in tumor microenvironment (TME) and clinical prediction significance in OV remained to be elucidated.\nMETHODS: The transcriptome data of high-grade serous OV from The Cancer Genome Atlas (TCGA) database were downloaded. Molecular subtypes were classified based on ferroptosis-correlated genes from the FerrDb database by performing consensus clustering analysis. The associations between the subtypes and clinicopathologic characteristics, mutation, regulatory pathways and immune landscape were assessed. A ferroptosis-related prognostic model was constructed and verified using International Cancer Genome Consortium (ICGC) cohort and GSE70769.\nRESULTS: Three molecular subtypes of OV were defined. Patients in subtype C3 tended to have the most favorable prognosis, while subtype C1 showing more mesenchymal cells, increased immune infiltration of Macrophages_M2, lower tumor purity, and epithelial-to-mesenchymal transition (EMT) features had the poorest prognosis. A ferroptosis-related risk model was constructed using 8 genes (PDP1, FCGBP, EPHA4, GAS1, SLC7A11, BLOC1S1, SPOCK2, and CXCL9) and manifested a strong prediction performance. High-risk patients had enriched EMT pathways, more Macrophages_M2, less plasma cells and CD8 cell infiltration, greater tendency of immune escape and worse prognosis. The risk score has negatively correlated relation with LAG3, TIGIT, CTLA4, IDO1, CD27, ICOS, and IL2RB but positively correlated with PVR, CD276, and CD28. Moreover, low-risk patients were more sensitive to Cisplatin and Gefitinib, Gemcitabine.\nCONCLUSIONS: Our results could improve the understanding of ferroptosis in OV, providing promising insights for the clinical targeted therapy for the cancer.", "claims": [{"id": "claim-method", "statement": "Ferroptosis-related genes (with P < 0.05) in TCGA-OV were identified by univariate Cox analysis from the expression profile matrix using the coxph function in R.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38795391", "locator": "sections[4] \"Identification of ferroptosis-based subtypes\" paragraph 2", "quote": "Ferroptosis-related genes (with P < 0.05) in TCGA-OV were identified by univariate Cox analysis from the expression profile matrix using the coxph function in R."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data that support the findings of this study are openly available in The Cancer Genome Atlas (TCGA, https://portal.gdc.cancer.gov/), Gene-Expression Omnibus (GEO, https://www.ncbi.nlm.nih.gov/geo/), and International Cancer Genome Consortium (ICGC, https://icgc.org). The experimental data can be obtained from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38795391", "locator": "sections[19] \"Data availability statement\" paragraph 2", "quote": "The data that support the findings of this study are openly available in The Cancer Genome Atlas (TCGA, https://portal.gdc.cancer.gov/), Gene-Expression Omnibus (GEO, https://www.ncbi.nlm.nih.gov/geo/), and International Cancer Genome Consortium (ICGC, https://icgc.org). The experimental data can be obtained from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Subtype C3 had the optimal prognosis, whereas subtype C1 had worse survival in the TCGA-OV cohort.", "kind": "quantitative", "target": {"value": 0.0069, "unit": "p-value", "tolerance": null, "source": "From KM curves, it could be observed that subtype C3 had the optimal prognosis and subtype C1 had the worse survival in TCGA-OV cohort (P = 0.0069) (Figure 1D)."}, "evidence": [{"asset": "source:pmid:38795391", "locator": "sections[21] \"Classification of three ferroptosis subtypes\" paragraph 2", "quote": "From KM curves, it could be observed that subtype C3 had the optimal prognosis and subtype C1 had the worse survival in TCGA-OV cohort (P = 0.0069) (Figure 1D)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Subtype C3 had the optimal prognosis, whereas subtype C1 had worse survival in the TCGA-OV cohort.", "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:38795391"], "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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