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pmid:34611432
Evaluation of Ferroptosis-related Gene AKR1C1 as a Novel Biomarker Associated with the Immune Microenvironment and Prognosis in Breast Cancer.
Zeyu Zhang · Xiangyuan Qiu · Yuanliang Yan · Qiujiu Liang · Yuan Cai · Bi Peng · Zhijie Xu · Fada Xia
International journal of general medicine · 2021 doi:10.2147/IJGM.S329031
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Experiment
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Complete file
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It has been increasingly recognized that ferroptosis-related genes participate in oncogenesis and development of cancers, including breast cancer (BRCA). Thus, It is important to explore the biofunctions of ferroptosis-related genes in BRCA.\nMETHODS: Transcriptome microarray datasets (GSE22358, GSE9014 and GSE8977, GSE2990 and GSE2034) and TCGA-BRCA were retrieved for analyses. And a variety of computational tools were used to identify the roles and associated biological functions in BRCA.\nRESULTS: Two ferroptosis-related genes (AKR1C1 and AKR1C3) were significantly expressed in GSE22358, GSE9014 and GSE8977. Higher expression of AKR1C1 was related with favorable prognosis. TCGA-BRCA further confirmed the expression of AKR1C1 and the prognostic value of AKR1C1. Co-expression analyses showed the most enriched GO term and KEGG pathways were termination of DNA-templated transcription and Fanconi anemia pathway. Subsequently, immunological analyses showed AKR1C1 was significantly associated with various immune infiltration cells; among these, dendritic cells, neutrophils, macrophages were the top three infiltrating cells. Furthermore, AKR1C1 was also associated with multiple immunostimulatory molecules and chemokines, including PD-1, PD-L1, CTLA4, B7-H3, VSIR, IL-6, BTLA, CXCL2, and CCR7. These results indicated the potential roles of AKR1C1 in the immune reaction during the pathogenesis of breast cancer.\nCONCLUSION: This study firstly demonstrated that ferroptosis-related gene, AKR1C1, could be associated with immune microenvironment, thereby influencing the development and prognosis of patient with breast cancer.", "claims": [{"id": "claim-method", "statement": "The expression of genes were compared using one-way ANOVA or Mann–Whitney U-test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34611432", "locator": "sections[3] \"Data Acquisition\" paragraph 2", "quote": "The expression of genes were compared using one-way ANOVA or Mann–Whitney U-test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data generated or analyzed during this study are included in this published article.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34611432", "locator": "sections[17] \"Data Sharing Statement\" paragraph 2", "quote": "All data generated or analyzed during this study are included in this published article."}], "state": "complete"}, {"id": "claim-target-result", "statement": "This study firstly demonstrated that ferroptosis-related gene, AKR1C1, could be associated with immune microenvironment, thereby influencing the development and prognosis of patient with breast cancer.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34611432", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "This study firstly demonstrated that ferroptosis-related gene, AKR1C1, could be associated with immune microenvironment, thereby influencing the development and prognosis of patient with breast cancer."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "This study firstly demonstrated that ferroptosis-related gene, AKR1C1, could be associated with immune microenvironment, thereby influencing the development and prognosis of patient with breast cancer.", "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:34611432"], "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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