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pmid:35866375
A ferroptosis-related gene signature for overall survival prediction and immune infiltration in lung squamous cell carcinoma.
Ti-Wei Miao · De-Qing Yang · Fang-Ying Chen · Qi Zhu · Xin Chen
Bioscience reports · 2022 doi:10.1042/BSR20212835
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Complete file
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However, the molecular mechanism and prognostic value of ferroptosis-related genes in lung squamous cell carcinoma (LUSC) are poorly understood.\nMETHODS: The mRNA expression profiles, methylation data, and clinical information of patients with LUSC were downloaded from TCGA and GEO database. Ferroptosis-related differentially expressed genes (DEGs) were identified between cancerous and non-cancerous tissues, and their prognostic value was systemically investigated by bioinformatic analyses.\nRESULTS: A ferroptosis-related gene signature (ALOX5, TFRC, PHKG2, FADS2, NOX1) was constructed using multivariate Cox regression analysis and represented as a risk score. Overall survival (OS) probability was significantly lower in the high-risk group than in the low-risk group (P<0.001), and receiver operating characteristic curve showed a good predictive capacity (AUC = 0.739). The risk score was an independent prognostic factor for LUSC. A nomogram was constructed to predict the OS probabilities at 1, 3, and 5 years. High-risk score was associated with increased immune infiltration, lower methylation levels, higher immune checkpoint genes expression levels, and better chemotherapy response. Cell adhesion molecules, focal adhesion, and extracellular matrix receptor interaction were the main pathways in the high-risk group. The signature was validated using the TCGA test cohort, entire TCGA cohort, GSE30219, GSE157010, GSE73403, and GSE4573 datasets. The gene disorders in patients with LUSC were validated using real-time PCR and single-cell RNA sequencing analysis.\nCONCLUSIONS: A ferroptosis-related gene signature was constructed to predict OS probability in LUSC. This could facilitate novel therapeutic methods and guide individualized therapy.", "claims": [{"id": "claim-method", "statement": "Multivariate Cox regression analysis was applied to construct the prognostic signature.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35866375", "locator": "sections[17] \"Construction of the prognostic signature\" paragraph 2", "quote": "Multivariate Cox regression analysis was applied to construct the prognostic signature."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data used to support the findings of the present study are available from TCGA database (https://portal.gdc.cancer.gov/) and GEO datasets (https://www.ncbi.nlm.nih.gov/gds/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35866375", "locator": "sections[30] \"Data Availability\" paragraph 2", "quote": "The data used to support the findings of the present study are available from TCGA database (https://portal.gdc.cancer.gov/) and GEO datasets (https://www.ncbi.nlm.nih.gov/gds/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A five-gene ferroptosis-related risk signature stratified LUSC patients by overall survival, with lower OS probability and an AUC of 0.739 in the high-risk group.", "kind": "quantitative", "target": {"value": 0.001, "unit": "p-value", "tolerance": null, "source": "Kaplan–Meier survival curve demonstrated that the high-risk group had a lower OS probability than the low-risk group (P<0.001; Figure 3A), and the area under the ROC curve (AUC) value was 0.739 (Figure 3B)."}, "evidence": [{"asset": "source:pmid:35866375", "locator": "sections[17] \"Construction of the prognostic signature\" paragraph 2", "quote": "Kaplan–Meier survival curve demonstrated that the high-risk group had a lower OS probability than the low-risk group (P<0.001; Figure 3A), and the area under the ROC curve (AUC) value was 0.739 (Figure 3B)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A five-gene ferroptosis-related risk signature stratified LUSC patients by overall survival, with lower OS probability and an AUC of 0.739 in the high-risk group.", "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:35866375"], "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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CON"], "order_basis": "paper_text_order:1684", "id": "assay:1"}, {"role": "data_generation", "definition_id": "scrna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "unsupported", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["LUSC were validated using real-time PCR and single-cell RNA sequencing analysis. CONCLUSIONS: A ferroptosis-related"], "order_basis": "paper_text_order:1703", "id": "assay:2"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["alidated using real-time PCR and single-cell RNA sequencing analysis. CONCLUSIONS: A ferroptosis-related"], "order_basis": "paper_text_order:1714", "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": ["Multivariate Cox regression analysis was applied to construct the prognostic signature."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}