Identification of a Ferroptosis-Related Long Noncoding RNA Prognostic Signature and Its Predictive Ability to Immunotherapy in Hepatocellular Carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34745200", "kind": "science-record", "revision": 5, "content_hash": "sha256:f314c879d650fd27b55c41d2e820b0855cf63e24b9a7f35a809ed9eb852c9360", "created_at": "2026-11-01T17:36:25Z", "updated_at": "2026-11-01T22:47:49Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of a Ferroptosis-Related Long Noncoding RNA Prognostic Signature and Its Predictive Ability to Immunotherapy in Hepatocellular Carcinoma.", "doi": "10.3389/fgene.2021.682082", "pmid": "34745200", "authors": ["Liang Wang", "Xiangwei Ge", "Zifeng Zhang", "Yating Ye", "Ziyi Zhou", "Manhong Li", "Hongxiang Yan", "Lei Wu", "Qian Bai", "Jipeng Li", "Jun Zhu", "Yusheng Wang"], "journal": "Frontiers in genetics", "year": 2021, "abstract": "Background: Immune checkpoint blockers (ICBs) are increasingly being used to treat patients with advanced hepatocellular carcinoma (HCC), but only a third of these patients are sensitive to ICBs. Emerging evidence suggests that ferroptosis could be a novel target for antitumor treatment, and combined treatment with ferroptosis inducers might enhance sensitivity to immunotherapy. However, there is a lack of information on the crosstalk between ferroptosis-related lncRNAs and anti-tumor immunity. Therefore, we aim to explore prognostic value of ferroptosis-related lncRNAs and clarify potential role in ICBs of HCC. Methods: We obtained mRNA and lncRNA expression data from two independent cohorts (TCGA and GEO database). Univariate Cox, the least absolute shrinkage and selection operator (Lasso) algorithm and multivariate Cox analysis were used to construct a lncRNA signature, which was evaluated using the area under the receiver operating characteristic curve (AUC) and Kaplan-Meier curves. Tumor-infiltrating cell (TIC) profiling and the tumor immune dysfunction and exclusion (TIDE) algorithm were used to validate the signature model and immunotherapy. Finally, we adopted RT-PCR assay to evaluate the differential expression of lncRNAs in HCC tissues in our hospital. Results: The ferroptosis-related lncRNA signature included five lncRNAs, most of which were positively correlated with clinical stage and grade. The signature could stratify patients into two risk groups, with the high-risk group associated with a shorter overall survival (OS, p < 0.05) in TCGA-LIHC and GSE76427. Besides, the AUCs of the 1-, 3-, and 5-years OS were 0.772, 0.707, and 0.666, respectively. Gene set enrichment analysis (GESA) of lncRNAs revealed enrichment of oncogenic and immune-related pathways. The TIC profiling indicated a close correlation between the signature and immune cells. Furthermore, the high-risk group had a better response to immunotherapy than low-risk group. RT-PCR demonstrated these five lncRNAs were upregulated in cancerous tissue than normal tissues. Conclusions: The ferroptosis-related lncRNA signature could accurately predict the OS of HCC patients and may serve as an independent clinical factor for patients' outcomes. Ferroptosis-related lncRNAs may remodel the tumor microenvironment (TME) and affect the anti-cancer ability of ICBs, and therefore, could potentially act as an indicator for the response to immunotherapy in HCC.", "claims": [{"id": "claim-method", "statement": "To validate the predictive value of the ferroptosis-related lncRNA signature, we used univariate Cox proportional hazard regression analysis and determined 78 prognosis-related lncRNAs. Subsequently, we incorporated 78 prognosis-related lncRNAs into the least absolute shrinkage and selection operator (Lasso) method.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34745200", "locator": "sections[5] \"Construction and Verification of a Ferroptosis-Related lncRNA Prognostic Signature (Fer-LPS)\" paragraph 2", "quote": "To validate the predictive value of the ferroptosis-related lncRNA signature, we used univariate Cox proportional hazard regression analysis and determined 78 prognosis-related lncRNAs. Subsequently, we incorporated 78 prognosis-related lncRNAs into the least absolute shrinkage and selection operator (Lasso) method."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34745200", "locator": "sections[19] \"Data Availability Statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The Fer-LPS risk score stratified HCC patients by overall survival and achieved time-dependent AUCs of 0.772, 0.707, and 0.666 at 1, 3, and 5 years.", "kind": "quantitative", "target": {"value": 0.0001, "unit": "p-value", "tolerance": null, "source": "The K-M curve indicated that high-risk group patients experienced a significantly worse OS than their low-risk counterparts (Figure 1B, p < 0.0001)."}, "evidence": [{"asset": "source:pmid:34745200", "locator": "sections[12] \"Construction of the Fer-LPS in Hepatocellular Carcinoma Survival\" paragraph 5", "quote": "The K-M curve indicated that high-risk group patients experienced a significantly worse OS than their low-risk counterparts (Figure 1B, p < 0.0001)."}, {"asset": "source:pmid:34745200", "locator": "sections[12] \"Construction of the Fer-LPS in Hepatocellular Carcinoma Survival\" paragraph 5", "quote": "The predictive performance of the risk score for OS was evaluated by time-dependent ROC curves, and the AUC reached 0.772 at 1 year, 0.707 at 3 years, and 0.666 at 5 years (Figure 1C)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The Fer-LPS risk score stratified HCC patients by overall survival and achieved time-dependent AUCs of 0.772, 0.707, and 0.666 at 1, 3, and 5 years.", "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:34745200"], "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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