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pmid:34761566
The roles of ferroptosis regulatory gene SLC7A11 in renal cell carcinoma: A multi-omics study.
Fangshi Xu · Yibing Guan · Li Xue · Peng Zhang · Mingrui Li · Mei Gao · Tie Chong
Cancer medicine · 2021 doi:10.1002/cam4.4395
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Experiment
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Complete file
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However, its function in renal cell carcinoma (RCC) remains elusive.\nMETHODS: The expression and somatic mutation information of SLC7A11 in RCC samples were determined using The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), Gene Expression Omnibus (GEO), Oncomine, and cBioPortal databases. The prognostic value of SLC7A11 was assessed through survival analysis, Receiver operating characteristic curve (ROC) analysis, independent prognostic analysis, clinical subgroup analysis, and nomogram. Its prognostic value was also validated in the ICGC and GSE29607 cohorts. Gene set enrichment analysis (GSEA) was employed to investigate the effects of SLC7A11 on multiple metabolic pathways. The CIBERSORT algorithm and single-sample gene set enrichment analysis (ssGSEA) method were applied to evaluate the effects of SLC7A11 on the tumor immune microenvironment (TIM). SLC7A11's therapeutic correlations were analyzed using the GSE87121, GSE67501, and GSDC datasets. Finally, the biofunctions of SLC7A11 in renal cancer cells and ferroptosis were ascertained by MTT, wound healing, transwell, and western blot assays.\nRESULTS: Through multiple datasets, SLC7A11 was found to be markedly upregulated in RCC. In terms of prognosis, SLC7A11 overexpression conferred a worse prognosis and was identified as an independent prognostic factor. Its prognostic value was validated in ICGC cohort. Moreover, high SL7CA11 expression could stimulate nucleotides, fatty acids, and amino acid metabolism to meet the proliferative consumption of tumor cells. As for the immune effect, SLC7A11 suppressed antitumor immunity by reducing the abundances of CD8+ T and NK cells. Regarding the therapeutic response, SLC7A11 expression was not correlated with the sensitivities of most chemotherapy and targeted drugs. Finally, SLC7A11 promoted the proliferation, migration, and invasion of renal cancer cells by enhancing GPX4 output, which in turn inhibits ferroptosis.\nCONCLUSIONS: SLC7A11 not only deeply influences RCC prognosis and TIM, but also promotes RCC progression by inhibiting ferroptosis and inducing metabolic reprogramming. In addition, SLC7A11 weakly affects the therapeutic effect and sensitivities of multiple chemotherapy and targeted drugs.", "claims": [{"id": "claim-method", "statement": "Cox univariate and multivariate analyses were successively conducted to identify the independent prognostic factors of RCC.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34761566", "locator": "sections[5] \"Prognostic analyses\" paragraph 2", "quote": "Cox univariate and multivariate analyses were successively conducted to identify the independent prognostic factors of RCC."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34761566", "locator": "sections[32] \"DATA AVAILABILITY STATEMENT\" paragraph 2", "quote": "The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "High SLC7A11 expression conferred a poor prognosis, leading to a 3-year survival rate of 62.9%, whereas that of low SLC7A11 expression was 76.2%.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34761566", "locator": "sections[19] \"SLC7A11 provides valuable information for RCC prognostic assessment\" paragraph 2", "quote": "High SLC7A11 expression conferred a poor prognosis, leading to a 3‐year survival rate of 62.9%, whereas that of low SLC7A11 expression was 76.2% (Figure 3A)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "High SLC7A11 expression conferred a poor prognosis, leading to a 3-year survival rate of 62.9%, whereas that of low SLC7A11 expression was 76.2%.", "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:34761566"], "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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