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pmid:35371305
Identification and analysis of a prognostic ferroptosis and iron-metabolism signature for esophageal squamous cell carcinoma.
Mengnan Zhao · Ming Li · Yuansheng Zheng · Zhengyang Hu · Jiaqi Liang · Guoshu Bi · Yunyi Bian · Qihai Sui · Cheng Zhan · Miao Lin · Qun Wang
Journal of Cancer · 2022 doi:10.7150/jca.68568
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Complete file
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Methods: The association of iron metabolism and ferroptosis-related genes with the prognosis, copy number variation (CNV), TMB, and immune cell infiltration of ESCC was explored using data from the GEO and TCGA database and validated by immunofluorescence in 112 ESCC patients from our center. The potential anti-cancer drugs and compounds from the GDSC and the Connectivity Map database were also screened. Results: A total of 117 iron metabolism and ferroptosis-related genes were identified. We found the expressions of PRNP, SLC3A2, SLC39A8, and SLC39A14 negatively related to the prognosis of ESCC patients, while ATP6V0A1 and LCN2 were opposite, which was validated in 112 ESCC samples from our center. And a prognostic signature was constructed based on their expressions and Cox regression coefficient (β). The low-score group exhibited a significantly worse OS. Besides, analysis of 179 ESCC samples from GSE53625 revealed that patients of poorly differentiation, more than 60 years, T4 stage, advanced N stage, advanced stage, and adjuvant therapy also exhibited a significantly shorter OS, based on which a nomogram to predict the OS was established. Moreover, the low-score group exhibited significantly higher CNV and TMB and more frequent mutations of TP53, MUC16, and NOTCH1. Higher proportion of Macrophages M2, and lower proportion of T cells follicular helper were observed in the low-score group. We discovered that AZD7762, Sunitinib, Cytarabine, Docetaxel, Vinblastine, and Elesclomol exhibited lower IC50 in the low-score group. And 20 potential compounds were identified from the CMap database. Conclusions: Six iron metabolism and ferroptosis-related genes were associated with the prognosis, CNV, TMB, and immune cell infiltration of ESCC. Some potential anti-cancer drugs and compounds may be helpful for OS.", "claims": [{"id": "claim-method", "statement": "The relation of the expression of DEGs to the prognosis of ESCC patients was analyzed with multivariate Cox regression, based on which a prognostic signature was constructed.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35371305", "locator": "sections[6] \"Construction and functional analysis of iron metabolism and ferroptosis-related prognostic signature\" paragraph 2", "quote": "The relation of the expression of DEGs to the prognosis of ESCC patients was analyzed with multivariate Cox regression, based on which a prognostic signature was constructed."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The expression data of ESCC and normal esophageal tissues were extracted from the GSE20347, GSE67269, and GSE38129 datasets.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35371305", "locator": "sections[5] \"Identifying differentially expressed iron metabolism and ferroptosis-related genes (DEGs) between ESCC and normal esophageal tissues\" paragraph 2", "quote": "The expression data of ESCC and normal esophageal tissues were extracted from the GSE20347, GSE67269, and GSE38129 datasets."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Six iron metabolism and ferroptosis-related genes were associated with the prognosis, CNV, TMB, and immune cell infiltration of ESCC.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35371305", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Conclusions: Six iron metabolism and ferroptosis-related genes were associated with the prognosis, CNV, TMB, and immune cell infiltration of ESCC."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Six iron metabolism and ferroptosis-related genes were associated with the prognosis, CNV, TMB, and immune cell infiltration of ESCC.", "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:35371305"], "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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T", "al cut-off score, based on which the 96 ESCC patients were divided into high- and low-score group. The"], "order_basis": "paper_text_order:2766", "id": "assay:1"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["g/gsea/index.jsp) 11. Cell culture and siRNA transfection Two ESCC cell lines (KYSE150 and ECA109) wer", "uangzhou, China) (Table S1). The siRNAs were transfected into cells with Lipo8000 transfect reagent (", "essions of the above 6 prognostic genes were knock-down with 2 diiferent small interfering RNAs (siR", "gdb.org/gsea/index.jsp) 11. 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