Single-cell transcriptomics uncover the key ferroptosis regulators contribute to cancer progression in head and neck squamous cell carcinoma

Liu, Fei; Tang, Lindong; Li, Qing; Chen, Leihui; Pan, Yuyue; Yin, Zhang; He, Jingjun; Tian, Junzhang

doi:10.3389/fmolb.2022.962742

Cited by 13 publications

(7 citation statements)

References 36 publications

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“…Their expression is higher in AML, and patients with high S100A8 have poor prognosis ( Laouedj et al, 2017 ; Mondet et al, 2021 ). S100A8 is reported to regulate autophagy-dependent ferroptosis in experimental subarachnoid hemorrhage ( Tao et al, 2022 ), and S100A9 may also play regulatory roles in ferroptosis but lack “wet” experimental validation in head and neck squamous cell carcinoma ( Liu et al, 2022 ). Increased KLF4 expression has been observed in AML and promotes disease progression ( Morris et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Molecular subtyping of acute myeloid leukemia through ferroptosis signatures predicts prognosis and deciphers the immune microenvironment

Fu,

Zhang,

et al. 2023

Front. Cell Dev. Biol.

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Acute myeloid leukemia (AML) is one of the most aggressive hematological malignancies with a low 5-year survival rate and high rate of relapse. Developing more efficient therapies is an urgent need for AML treatment. Accumulating evidence showed that ferroptosis, an iron-dependent form of programmed cell death, is closely correlated with cancer initiation and clinical outcome through reshaping the tumor microenvironment. However, understanding of AML heterogeneity based on extensive profiling of ferroptosis signatures remains to be investigated yet. Herein, five independent AML transcriptomic datasets (TCGA-AML, GSE37642, GSE12417, GSE10358, and GSE106291) were obtained from the GEO and TCGA databases. Then, we identified two ferroptosis-related molecular subtypes (C1 and C2) with distinct prognosis and tumor immune microenvironment (TIME) by consensus clustering. Patients in the C1 subtype were associated with favorable clinical outcomes and increased cytotoxic immune cell infiltration, including CD8+/central memory T cells, natural killer (NK) cells, and non-regulatory CD4+ T cells while showing decreased suppressive immune subsets such as M2 macrophages, neutrophils, and monocytes. Functional enrichment analysis of differentially expressed genes (DEGs) implied that cell activation involved in immune response, leukocyte cell–cell adhesion and migration, and cytokine production were the main biological processes. Phagosome, antigen processing and presentation, cytokine–cytokine receptor interaction, B-cell receptor, and chemokine were identified as the major pathways. To seize the distinct landscape in C1 vs. C2 subtypes, a 5-gene prognostic signature (LSP1, IL1R2, MPO, CRIP1, and SLC24A3) was developed using LASSO Cox stepwise regression analysis and further validated in independent AML cohorts. Patients were divided into high- and low-risk groups, and decreased survival rates were observed in high- vs. low-risk groups. The TIME between high- and low-risk groups has a similar scenery in C1 vs. C2 subtypes. Single-cell-level analysis verified that LSP1 and CRIP1 were upregulated in AML and exhausted CD8+ T cells. Dual targeting of these two markers might present a promising immunotherapeutic for AML. In addition, potential effective chemical drugs for AML were predicted. Thus, we concluded that molecular subtyping using ferroptosis signatures could characterize the TIME and provide implications for monitoring clinical outcomes and predicting novel therapies.

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Section: Discussionmentioning

confidence: 99%

Molecular subtyping of acute myeloid leukemia through ferroptosis signatures predicts prognosis and deciphers the immune microenvironment

Fu,

Zhang,

et al. 2023

Front. Cell Dev. Biol.

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“…Meanwhile, previous report also indicated that the heterogeneity of epithelial-derived cells and immune cells is the main reason for the heterogeneity of laryngeal carcinoma. 26 , 27 …”

Section: Discussionmentioning

confidence: 99%

Exploration of the heterogeneity and interaction of epithelial cells and NK/T-cells in Laryngeal Squamous Cell Carcinoma based on single-cell RNA sequencing data

Liu¹,

Gao²,

Peng³

et al. 2023

Brazilian Journal of Otorhinolaryngology

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“…Therefore, the inactivation of ACSL4, LPCAT3, or ACC inhibits the progression of tumour cell ferroptosis [ 76 – 78 ]. Recent studies have shown that in HNSCC, the expression levels of the ACSL1 and TFRC genes are closely related to the occurrence of tumour cell ferroptosis and the prognosis of patients and are potential targets for the occurrence, development and treatment of HNSCC [ 79 ]. The high expression of acyl-CoA synthetase long-chain family member 1 (ACSL1) inhibits the progression of thyroid cancer cells and activates fatty acid metabolism reprogramming during cancer cell metastasis, thereby achieving an antagonizing effect of ferroptosis on tumour cells [ 79 – 81 ].…”

Section: Mechanisms Of Cell Death In Hnsccmentioning

confidence: 99%

“…TFRCs are key transporters of intracellular iron and play a key role in tumour cell ferroptosis through their regulation by the NF2-YAP signalling axis. High expression of TFRC is associated with poor prognosis in patients with HNSCC [ 79 , 82 ]. Compared with the levels in normal tissues, the ferroptosis driver SOCS1 and inhibitor FTH1 in HNSCC were positively correlated and upregulated.…”

Section: Mechanisms Of Cell Death In Hnsccmentioning

confidence: 99%

Effect of regulatory cell death on the occurrence and development of head and neck squamous cell carcinoma

et al. 2023

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Head and neck cancer is a malignant tumour with a high mortality rate characterized by late diagnosis, high recurrence and metastasis rates, and poor prognosis. Head and neck squamous cell carcinoma (HNSCC) is the most common type of head and neck cancer. Various factors are involved in the occurrence and development of HNSCC, including external inflammatory stimuli and oncogenic viral infections. In recent years, studies on the regulation of cell death have provided new insights into the biology and therapeutic response of HNSCC, such as apoptosis, necroptosis, pyroptosis, autophagy, ferroptosis, and recently the newly discovered cuproptosis. We explored how various cell deaths act as a unique defence mechanism against cancer emergence and how they can be exploited to inhibit tumorigenesis and progression, thus introducing regulatory cell death (RCD) as a novel strategy for tumour therapy. In contrast to accidental cell death, RCD is controlled by specific signal transduction pathways, including TP53 signalling, KRAS signalling, NOTCH signalling, hypoxia signalling, and metabolic reprogramming. In this review, we describe the molecular mechanisms of nonapoptotic RCD and its relationship to HNSCC and discuss the crosstalk between relevant signalling pathways in HNSCC cells. We also highlight novel approaches to tumour elimination through RCD.

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Single-cell transcriptomics uncover the key ferroptosis regulators contribute to cancer progression in head and neck squamous cell carcinoma

Cited by 13 publications

References 36 publications

Molecular subtyping of acute myeloid leukemia through ferroptosis signatures predicts prognosis and deciphers the immune microenvironment

Molecular subtyping of acute myeloid leukemia through ferroptosis signatures predicts prognosis and deciphers the immune microenvironment

Exploration of the heterogeneity and interaction of epithelial cells and NK/T-cells in Laryngeal Squamous Cell Carcinoma based on single-cell RNA sequencing data

Effect of regulatory cell death on the occurrence and development of head and neck squamous cell carcinoma

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