Identification and Validation of a Novel Ferroptotic Prognostic Genes-Based Signature of Clear Cell Renal Cell Carcinoma.

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Differing from other cell deaths (such as apoptosis, necroptosis, pyroptosis, and autophagy), ferroptosis is characterized by iron-dependence, polyunsaturated fatty acid oxidization, and lipid peroxide accumulation. We analyzed the ferroptosis database (FerrDb V2), Gene Expression Omnibus database, The Cancer Genome Atlas database, and the ArrayExpress database. Nine genes that were differentially expressed and related to prognosis were involved in the ferroptotic prognostic model via the least absolute shrinkage and selection operator Cox regression analysis, which was established in ccRCC patients from the kidney renal clear cell carcinoma (KIRC) cohort in TCGA database, and validated in ccRCC patients from the E-MTAB-1980 cohort in the ArrayExpress database. The signature could be an independent prognostic factor for ccRCC, and high-risk patients showed worse overall survival. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were utilized to investigate the potential mechanisms. The nine genes in ccRCC cells with erastin or RSL3 treatment were validated to find the crucial gene. The glutaminase 2 (GLS2) gene was upregulated during ferroptosis in ccRCC cells, and cells with GLS2 shRNA displayed lower survival, a lower glutathione level, and a high lipid peroxide level, which illustrated that GLS2 might be a ferroptotic suppressor in ccRCC.", "claims": [{"id": "claim-method", "statement": "The LASSO Cox regression analysis was used to select ferroptotic prognostic DEGs (FPEDGs) using the “glmnet” package, and the optimal lambda (λ) was identified as the optimal value through a tenfold cross-validation process [28,29].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36230613", "locator": "sections[4] \"2.2. Establishment and Validation of the FPM\" paragraph 2", "quote": "The LASSO Cox regression analysis was used to select ferroptotic prognostic DEGs (FPEDGs) using the “glmnet” package, and the optimal lambda (λ) was identified as the optimal value through a tenfold cross-validation process [28,29]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data used in this study are available from the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36230613", "locator": "sections[34] \"Data Availability Statement\" paragraph 2", "quote": "The data used in this study are available from the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The ferroptosis prognostic model was a suitable prognostic predictor for ccRCC, with time-dependent ROC AUCs of 0.751 at 1 year, 0.732 at 3 years, and 0.748 at 5 years.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36230613", "locator": "sections[20] \"3.2. Construction of the FPM in TCGA\" paragraph 4", "quote": "Furthermore, the time-dependent ROC analysis was utilized to show the prognostic value and predictive performance of the FPM, and the area under curve (AUC) reached 0.751 at 1 year, 0.732 at 3 years, and 0.748 at 5 years (Figure 3G), which illustrated that the FPM could be a suitable prognostic predictor."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The ferroptosis prognostic model was a suitable prognostic predictor for ccRCC, with time-dependent ROC AUCs of 0.751 at 1 year, 0.732 at 3 years, and 0.748 at 5 years.", "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:36230613"], "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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