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pmid:35935576
Systematic Construction and Validation of a Novel Ferroptosis-Related Gene Model for Predicting Prognosis in Cervical Cancer.
Wentao Qin · Can He · Daqiong Jiang · Yang Gao · Yu Chen · Min Su · Yuanjun Yang · Zhao Yang · Hongbing Cai · Hua Wang
Journal of immunology research · 2022 doi:10.1155/2022/2148215
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Complete file
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The \"NMF\" R package was conducted to calculate the matrix of the screened prognosis gene expression. Ferroptosis-related differential genes in cervical cancer were detected using the \"limma\" R function and WGCNA. The least absolute shrinkage and selection operator (LASSO) algorithm and Cox regression analysis were conducted to develop a novel prognostic signature. The prediction model was verified by the nomogram integrating clinical characteristics; the GSE44001 dataset was used as an external verification. Then, the immune status and tumor mutation load were explored. Finally, immunohistochemistry as well as quantitative polymerase chain reaction (RT-qPCR) was utilized to ascertain the expression of FRGs.\nResults: Two molecular subgroups (cluster 1 and cluster 2) with different FRG expression patterns were recognized. A ferroptosis-related model based on 4 genes (VEGFA, CA9, DERL3, and RNF130) was developed through TCGA database to identify the unfavorable prognosis cases. Patients in cluster 1 showed significantly decreased overall survival in contrast with those in cluster 2 (P < 0.05). The LASSO technique and Cox regression analysis were both utilized to establish the independence of the prognostic model. The validity of nomogram prognostic predictions has been well demonstrated for 3- and 5-year survival in both internal and external data validation cohorts. These two subgroups showed striking differences in tumor-infiltrating leukocytes and tumor mutation burden. The low-risk subgroup showed a longer overall survival time with a higher immune cell score and higher tumor mutation rate. Gene functional enrichment analyses revealed predominant enrichment in various tumor-associated signaling pathways. Finally, the expression of each gene was confirmed by immunohistochemistry and RT-qPCR.\nConclusion: A novel and comprehensive ferroptosis-related gene model was proposed for cervical cancer which was capable of distinguishing the patients independently with high risk for poor survival, and targeting ferroptosis may represent a promising approach for the treatment of CC.", "claims": [{"id": "claim-method", "statement": "The least absolute shrinkage and selection operator (LASSO) algorithm and Cox regression analysis were conducted to develop a novel prognostic signature.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35935576", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The least absolute shrinkage and selection operator (LASSO) algorithm and Cox regression analysis were conducted to develop a novel prognostic signature."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data used in this research come from open online databases, which included the GEO (https://www.ncbi.nlm.nih.gov/geo/) and TCGA (https://portal.gdc.cancer.gov/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35935576", "locator": "sections[27] \"Data Availability\" paragraph 2", "quote": "The data used in this research come from open online databases, which included the GEO (https://www.ncbi.nlm.nih.gov/geo/) and TCGA (https://portal.gdc.cancer.gov/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Additionally, after plotting the receiver operating characteristic (ROC) curves, we found that the values of the area under the curve (AUC) were 0.737, 0.734, and 0.706 over 1, 3, and 5 years correspondingly (Figure 4(b)).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35935576", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "A ferroptosis-related model based on 4 genes (VEGFA, CA9, DERL3, and RNF130) was developed through TCGA database to identify the unfavorable prognosis cases."}, {"asset": "source:pmid:35935576", "locator": "sections[16] \"3.3. 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Finally, immunohistochemistry as well as quantitative polymerase chain rea", "the expression of each gene was confirmed by immunohistochemistry and RT-qPCR. Conclusion: A novel and compreh"], "order_basis": "paper_text_order:832", "id": "assay:2"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["l as quantitative polymerase chain reaction (RT-qPCR) was utilized to ascertain the expression of", "ne was confirmed by immunohistochemistry and RT-qPCR. Conclusion: A novel and comprehensive ferro", "s quantitative polymerase chain reaction (RT-qPCR) was utilized to ascertain the expression of", "was confirmed by immunohistochemistry and RT-qPCR. Conclusion: A novel and comprehensive ferro"], "order_basis": "paper_text_order:903", "id": "assay:3"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The least absolute shrinkage and selection operator (LASSO) algorithm and Cox regression analysis were conducted to develop a novel prognostic signature."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}