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pmid:34715817

Ferroptosis regulators, especially SQLE, play an important role in prognosis, progression and immune environment of breast cancer.

Wenqing Tang · Fangshi Xu · Meng Zhao · Shuqun Zhang

BMC cancer · 2021 doi:10.1186/s12885-021-08892-4

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title
Ferroptosis regulators, especially SQLE, play an important role in prognosis, progression and immune environment of breast cancer.
doi
10.1186/s12885-021-08892-4
pmid
34715817
authors array · 4 items
[0]
Wenqing Tang
[1]
Fangshi Xu
[2]
Meng Zhao
[3]
Shuqun Zhang
journal
BMC cancer
year
2021
abstract
BACKGROUND: Ferroptosis, a new form of programmed cell death, has great potential for cancer treatment. However, the roles of ferroptosis-related (FR) genes in breast cancer (BC) remain elusive. MATERIALS AND METHODS: Using TCGA database, a novel FR risk signature was constructed through the Lasso regression analysis. Meanwhile, its prognostic value was assessed by a series of survival analyses. Besides, a nomogram was constructed to predict the overall survival rate (OSR) of individual at 1,3,5 year. Four validation cohorts (n = 2248), including METABRIC, GSE58812, GSE20685 and ICGC-KR datasets, were employed to test the prognostic value of FR risk signature. The effects of FR risk signature on BC immune microenvironment were explored by CIBERSORT algorithm and ssGSEA method. The histological expressions of FR risk genes were presented by HPA database. The biofunctions of SQLE were determined by qPCR, MTT, wound-healing and Transwell assays. RESULTS: We constructed a novel FR risk signature consisting of eight genes. High FR risk led a poor prognosis and was identified as an independent prognostic factor. Besides, A higher proportion of patients with luminal A type was observed in low-risk group (53%), while a higher proportion of patients with basal type in high-risk group (24%). FR risk score could discriminate the prognostic difference of most clinical subgroups, except for M1 stage, HER2 and basal types. Moreover, its prognostic value was successfully validated in other four cohorts. Through immune analyses, we found that the reduced infiltration levels of CD8+ and NK cells, whereas the enhanced activity of antigen presentation process appeared in high FR risk. Then, FR risk score was found to weakly correlate with the expressions of six immune checkpoints. Through the experiments in vitro, we confirmed that overexpression of SQLE could promote, whereas blocking SQLE could inhibit the proliferative, migrative and invasive abilities of BC cells. CONCLUSIONS: FR risk signature was conducive to BC prognostic assessment. High FR risk level was closely associated with BC immunosuppression, but may not predict ICIs efficacy. Moreover, SQLE was identified as a crucial cancer-promoting gene in BC. Our findings provide new insights into prognostic assessment and molecular mechanism of BC.
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Using TCGA database, a novel FR risk signature was constructed through the Lasso regression analysis.
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The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request. All databases in the present study are open, as follows: TCGA database (https://portal.gdc.cancer.gov/), GEO database (https://www.ncbi.nlm.nih.gov/geo/), ICGC database (http://dcc.icgc.org/), METABRIC cohort (http://www.cbioportal.org/), FerrDB database (http://www.zhounan.org/ferrdb/), MSigDB database (https://www.gsea-msigdb.org/gsea/msigdb/) and HPA database (http://www.proteinatlas.org/).
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The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request. All databases in the present study are open, as follows: TCGA database (https://portal.gdc.cancer.gov/), GEO database (https://www.ncbi.nlm.nih.gov/geo/), ICGC database (http://dcc.icgc.org/), METABRIC cohort (http://www.cbioportal.org/), FerrDB database (http://www.zhounan.org/ferrdb/), MSigDB database (https://www.gsea-msigdb.org/gsea/msigdb/) and HPA database (http://www.proteinatlas.org/).
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Using TCGA database, a novel FR risk signature was constructed through the Lasso regression analysis.
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Using TCGA database, a novel FR risk signature was constructed through the Lasso regression analysis.
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title
Gene-expression molecular subtyping of triple-negative breast cancer tumours: importance of immune response
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The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request. All databases in the present study are open, as follows: TCGA database (https://portal.gdc.cancer.gov/), GEO database (https://www.ncbi.nlm.nih.gov/geo/), ICGC database (http://dcc.icgc.org/), METABRIC cohort (http://www.cbioportal.org/), FerrDB database (http://www.zhounan.org/ferrdb/), MSigDB database (https://www.gsea-msigdb.org/gsea/msigdb/) and HPA database (http://www.proteinatlas.org/).
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iofunctions of SQLE were determined by qPCR, MTT, wound-healing and Transwell assays. RESULTS
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Materials and methods Cell culture and transfection One normal human breast cell line (MCF-10A)
[1]
Lipofectamine™ 2000 was employed to perform transfection (Thermo Fisher Scientific, Waltham, MA, USA)
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34715817", "kind": "science-record", "revision": 4, "content_hash": "sha256:6a4ed6043273a07f338710d011466d3e9e8a096dcb51abf4c702832f61b2a406", "created_at": "2026-11-01T17:36:23Z", "updated_at": "2026-11-01T22:05:03Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Ferroptosis regulators, especially SQLE, play an important role in prognosis, progression and immune environment of breast cancer.", "doi": "10.1186/s12885-021-08892-4", "pmid": "34715817", "authors": ["Wenqing Tang", "Fangshi Xu", "Meng Zhao", "Shuqun Zhang"], "journal": "BMC cancer", "year": 2021, "abstract": "BACKGROUND: Ferroptosis, a new form of programmed cell death, has great potential for cancer treatment. However, the roles of ferroptosis-related (FR) genes in breast cancer (BC) remain elusive.\nMATERIALS AND METHODS: Using TCGA database, a novel FR risk signature was constructed through the Lasso regression analysis. Meanwhile, its prognostic value was assessed by a series of survival analyses. Besides, a nomogram was constructed to predict the overall survival rate (OSR) of individual at 1,3,5 year. Four validation cohorts (n = 2248), including METABRIC, GSE58812, GSE20685 and ICGC-KR datasets, were employed to test the prognostic value of FR risk signature. The effects of FR risk signature on BC immune microenvironment were explored by CIBERSORT algorithm and ssGSEA method. The histological expressions of FR risk genes were presented by HPA database. The biofunctions of SQLE were determined by qPCR, MTT, wound-healing and Transwell assays.\nRESULTS: We constructed a novel FR risk signature consisting of eight genes. High FR risk led a poor prognosis and was identified as an independent prognostic factor. Besides, A higher proportion of patients with luminal A type was observed in low-risk group (53%), while a higher proportion of patients with basal type in high-risk group (24%). FR risk score could discriminate the prognostic difference of most clinical subgroups, except for M1 stage, HER2 and basal types. Moreover, its prognostic value was successfully validated in other four cohorts. Through immune analyses, we found that the reduced infiltration levels of CD8+ and NK cells, whereas the enhanced activity of antigen presentation process appeared in high FR risk. Then, FR risk score was found to weakly correlate with the expressions of six immune checkpoints. Through the experiments in vitro, we confirmed that overexpression of SQLE could promote, whereas blocking SQLE could inhibit the proliferative, migrative and invasive abilities of BC cells.\nCONCLUSIONS: FR risk signature was conducive to BC prognostic assessment. High FR risk level was closely associated with BC immunosuppression, but may not predict ICIs efficacy. Moreover, SQLE was identified as a crucial cancer-promoting gene in BC. Our findings provide new insights into prognostic assessment and molecular mechanism of BC.", "claims": [{"id": "claim-method", "statement": "Using TCGA database, a novel FR risk signature was constructed through the Lasso regression analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34715817", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Using TCGA database, a novel FR risk signature was constructed through the Lasso regression analysis."}], "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. All databases in the present study are open, as follows: TCGA database (https://portal.gdc.cancer.gov/), GEO database (https://www.ncbi.nlm.nih.gov/geo/), ICGC database (http://dcc.icgc.org/), METABRIC cohort (http://www.cbioportal.org/), FerrDB database (http://www.zhounan.org/ferrdb/), MSigDB database (https://www.gsea-msigdb.org/gsea/msigdb/) and HPA database (http://www.proteinatlas.org/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34715817", "locator": "sections[32] \"Availability of data and materials\" paragraph 2", "quote": "The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request. All databases in the present study are open, as follows: TCGA database (https://portal.gdc.cancer.gov/), GEO database (https://www.ncbi.nlm.nih.gov/geo/), ICGC database (http://dcc.icgc.org/), METABRIC cohort (http://www.cbioportal.org/), FerrDB database (http://www.zhounan.org/ferrdb/), MSigDB database (https://www.gsea-msigdb.org/gsea/msigdb/) and HPA database (http://www.proteinatlas.org/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using TCGA database, a novel FR risk signature was constructed through the Lasso regression analysis.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34715817", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Using TCGA database, a novel FR risk signature was constructed through the Lasso regression analysis."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Using TCGA database, a novel FR risk signature was constructed through the Lasso regression analysis.", "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:34715817"], "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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All databases in the present study are open, as follows: TCGA database (https://portal.gdc.cancer.gov/), GEO database (https://www.ncbi.nlm.nih.gov/geo/), ICGC database (http://dcc.icgc.org/), METABRIC cohort (http://www.cbioportal.org/), FerrDB database (http://www.zhounan.org/ferrdb/), MSigDB database (https://www.gsea-msigdb.org/gsea/msigdb/) and HPA database (http://www.proteinatlas.org/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request. All databases in the present study are open, as follows: TCGA database (https://portal.gdc.cancer.gov/), GEO database (https://www.ncbi.nlm.nih.gov/geo/), ICGC database (http://dcc.icgc.org/), METABRIC cohort (http://www.cbioportal.org/), FerrDB database (http://www.zhounan.org/ferrdb/), MSigDB database (https://www.gsea-msigdb.org/gsea/msigdb/) and HPA database (http://www.proteinatlas.org/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM519117", "GSM519118", "GSM519119", "GSM519120", "GSM519121", "GSM519122", "GSM519123", "GSM519124", "GSM519125", "GSM519126", "GSM519127", "GSM519128", "GSM519129", "GSM519130", "GSM519131", "GSM519132", "GSM519133", "GSM519134", "GSM519135", "GSM519136", "GSM519137", "GSM519138", "GSM519139", "GSM519140", "GSM519141", "GSM519142", "GSM519143", "GSM519144", "GSM519145", "GSM519146", "GSM519147", "GSM519148", "GSM519149", "GSM519150", "GSM519151", "GSM519152", "GSM519153", "GSM519154", "GSM519155", "GSM519156", 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RE"], "order_basis": "paper_text_order:997", "id": "assay:1"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["iofunctions of SQLE were determined by qPCR, MTT, wound-healing and Transwell assays. RESULTS"], "order_basis": "paper_text_order:1002", "id": "assay:2"}, {"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": ["Materials and methods Cell culture and transfection One normal human breast cell line (MCF-10A)", "Lipofectamine™ 2000 was employed to perform transfection (Thermo Fisher Scientific, Waltham, MA, USA)"], "order_basis": "paper_text_order:2457", "id": "assay:3"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["y Company (Wuhan, China). MCF-10A cells were cultured in Dulbecco’s Modified Eagle’s Medium (DMEM) co", "nicillin/Streptomycin (P/S). MCF7 cells were cultured in Minimum Essential Medium (MEM) containing 10", "ing 10%FBS and 1% P/S. MDA-MB-231 cells were cultured in Leibovitz’s L-15 medium containing 10%FBS an", "(MCF-10A) and two breast cancer cell lines (MCF7 and MDA-MB-231) were purchased from Procell"], "order_basis": "paper_text_order:2543", "id": "assay:4"}, {"role": "analysis", "definition_id": "principal_component_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["pca_fit"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["PCA"], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}