A signature of four ferroptosis-related genes in laryngeal squamous cell carcinoma
Open accessAbstract
Background: Laryngeal squamous cell carcinoma (LSCC) prognosis has not improved significantly in the past few decades, and more effective treatments are needed to be explored. Ferroptosis is a newly discovered kind of regulated cell death in recent years, which is related to tumor immunity and can used to treat tumors. Therefore, the prognostic value of ferroptosis-related genes in laryngeal cancer needs further clarification. Methods: In this study, the mRNA expression profile data of LSCC were downloaded from the public database. After identifying ferroptosis-related differentially expressed genes (FDGs), we explored the role of these genes through functional enrichment analysis. FDGs with prognostic significance were identified by univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses. By calculating the risk score, we constructed a prognostic model. Kaplan-Meier (K-M) analysis, the receiver operating characteristic (ROC) curves, and the nomogram were utilized to investigate this model. Public databases and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to verify the expression of model genes. Results: The model consisting of four FDGs was acknowledged to be a self-determining predictor of prognosis. The K-M survival curves and the ROC curves confirmed the model’s predictive ability. The C index (0.805) indicates that the nomogram has a good predictive ability. In vitro studies have confirmed the differential expression of the four FDGs. Conclusions: We identified a novel ferroptosis-related gene signature for predicting prognosis in LSCC.
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Increased PLIN4 expression increases ferroptosis in tumor cells, Leydig cells, and hippocampal neurons.
“emerging data has linked PLIN4 to ferroptosis with increased PLIN4 expression increasing ferroptosis in tumor cells [38], Leydig cells [39], and hippocampal neurons [40].”
From Astrocytic APOE3-Christchurch expression ameliorates brain amyloid-β pathology in 5xFAD mice (2026) · cites this paper as [38]
Citation [38] is attached to the tumor-cell portion of the sentence, not the separately cited Leydig-cell or hippocampal-neuron claims. The Discussion says PLIN4 may promote ferroptosis in a GSH-dependent manner and can be upregulated after treatment with a ferroptosis inducer. It does not establish that increased PLIN4 expression itself increases ferroptosis in tumor cells; the citing sentence presents that causal effect as certain and omits the condition. (LLM, conf=0.86)
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Cites
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NFS1 undergoes positive selection in lung tumours and protects cells from ferroptosis
Alvarez, S. W., Sviderskiy, V. O., Terzi, E. M., Papagiannakopoulos, T., Moreira, A. L., Adams, S., Sabatini, D. M., Birsoy, K., & Possemato, R. (2017) · Nature · doi:10.1038/nature24637 · Cited by 787 · see citing works
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Lu, B., Chen, X. B., Ying, M. D., He, Q. J., Cao, J., & Yang, B. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00992 · Cited by 444 · see citing works
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Cited by
Sorted by citations
Astrocytic APOE3-Christchurch expression ameliorates brain amyloid-β pathology in 5xFAD mice
Raulin, A.-C., Alnobani, A., Rodriguez-Martinez, P., Lee, E., Linares, C., Yslas, A. R., Li, M., Ren, Y., Doss, S. V., Roy, B., et al. (2026) · Translational Psychiatry · doi:10.1038/s41398-026-04002-9
- Authors
- Zhao, R., Chen, Q., Qiao, P., Lu, Y., & Chen, X.
- Affiliations
- Shanghai Pudong New Area Gongli Hospital (CN)
- Ningxia Medical University (CN)
- Shanghai University (CN)
- Corresponding author
- Chen, Xiaoping
- Venue
- Translational Cancer Research
- Publisher
- AME Publishing Company
- Published
- 2024-06
- Volume
- 13
- Issue
- 6
- Pages
- 2938-2949
- ISSN
- 2218-676X (ISSN-L)
- 2219-6803
- PMC
- PMC11231803
- OpenAlex
- W4399898615
- Cited by
- 3
- References
- 3
- Citations by year
- 2026: 2 · 2025: 1
- FWCI
- 0.87
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Translational Cancer Research (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Massachusetts Department of Agricultural Resources
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- laryngeal squamous cell carcinoma, ferroptosis, ferroptosis-related genes, prognostic gene signature, risk score, nomogram, differentially expressed genes, antitumor immunity, survival prediction
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