Systematic profiling of ferroptosis gene signatures predicts prognostic factors in esophageal squamous cell carcinoma

Lu, Tong; Xu, Ran; Li, Qi; Zhao, Jichun; Peng, Bo; Zhang, Han; Guo, Jida; Zhang, Shengqiang; Li, Huawei; Wang, Jun; Zhang, Lin-you

doi:10.1016/j.omto.2021.02.011

Cited by 49 publications

(43 citation statements)

References 41 publications

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“…We further demonstrated that the expression of GPX4 in tumorous specimens from esophageal cancer patients is correlated with a poor prognosis ( Figure 5 A,B). Our findings also support recent studies that identified ferroptosis-related gene signatures, which can be used to predict the prognosis and immunological responses of esophageal squamous cell carcinoma and other cancers [ 30 , 31 ].…”

Section: Discussionsupporting

confidence: 90%

Esophageal Cancer Stem-like Cells Resist Ferroptosis-Induced Cell Death by Active Hsp27-GPX4 Pathway

Liu

Lin

et al. 2021

Biomolecules

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Cancer stem cells (CSCs), a subpopulation of cancer cells responsible for tumor initiation and treatment failure, are more susceptible to ferroptosis-inducing agents than bulk cancer cells. However, regulatory pathways controlling ferroptosis, which can selectively induce CSC death, are not fully understood. Here, we demonstrate that the CSCs of esophageal squamous carcinoma cells enriched by spheroid culture have increased intracellular iron levels and lipid peroxidation, thereby increasing exposure to several products of lipid peroxidation, such as MDA and 4-HNE. However, CSCs do not reduce cell viability until glutathione is depleted by erastin treatment. Mechanistic studies revealed that damage from elevated lipid peroxidation is avoided through the activation of Hsp27, which upregulates GPX4 and thereby rescues CSCs from ferroptosis-induced cell death. Our results also revealed a correlation between phospho-Hsp27 and GPX4 expression levels and poor prognosis in patients with esophageal cancer. Together, these data indicate that targeting Hsp27 or GPX4 to block this intrinsic protective mechanism against ferroptosis is a potential treatment strategy for eradicating CSC in esophageal squamous cell carcinoma.

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Section: Discussionsupporting

confidence: 90%

Esophageal Cancer Stem-like Cells Resist Ferroptosis-Induced Cell Death by Active Hsp27-GPX4 Pathway

Liu

Lin

et al. 2021

Biomolecules

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“…Since extensive crossover between immunotherapy and non-apoptotic RCD mechanisms has been detected, non-apoptotic cancer cell death accompanied by immunomodulation is considered an exceedingly promising strategy for cancer treatment [ 28 ]. Ferroptosis, a neoteric form of RCD with unique biological and morphological features, has been shown to interact with the tumor immune response and can influence immunotherapeutic efficacy on the one hand [ 8 ], and in turn is regulated by immune cells on the other [ 7 ]. In the present study, based on ferroptosis-related genes in STS, we identified potential ICGs including PDCD1, CTLA4, TIGIT, IDO1 and CD27, which might serve as important targets for immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…Meanwhile, ferroptosis has exhibited great potential in the treatment of cancer and has gained widespread attention in STS as well [ 6 ]. Recent studies have revealed that ferroptosis and tumor immunity can be mutually regulated [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Immunological and prognostic significance of novel ferroptosis-related genes in soft tissue sarcoma

Zhao

et al. 2022

PLoS ONE

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Background Ferroptosis has exhibited great potential in the treatment of cancer and has gained widespread attention in soft tissue sarcoma (STS). The aim was to explore the immunological and prognostic significance of novel ferroptosis-related genes in STS. Methods We identified ferroptosis-related differentially expressed genes (DEGs) in STS to construct the networks of enrichment analysis and protein-protein interaction. Subsequently, hub genes with prognostic significance were localized and a series of prognostic and immune analyses were performed. Results 40 ferroptosis-related DEGs were identified, of which HELLS, STMN1 EPAS1, CXCL2, NQO1, and IL6 were classified as hub genes and were associated with the prognosis in STS patients. In the results of the immune analysis, PDCD1, CTLA4, TIGIT, IDO1 and CD27 exhibited consistent intense correlations as immune checkpoint genes, as well as macrophage, neutrophil, cytotoxic cell, dendritic cell, interdigitating dendritic cell and plasmacytoid dendritic cell as immune cells. EPAS1 and HELLS might be independent prognostic factors for STS patients, and separate prognostic models were constructed by using them. Conclusions We recognized novel ferroptosis-related genes with prognostic value in STS. Furthermore, we searched out potential immune checkpoints and critical immune cells.

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“…Previous studies have confirmed that KIRC is closely related to von Hippel-Lindau (VHL) gene changes ( Zhang et al, 2018 ; Zhang et al, 2020 ). In addition, ferroptosis-related genes, some miRNAs, and pathways also participate in regulating the process of KIRC regulation ( Lu et al, 2021 ; Zhang et al, 2021 ). Autophagy plays a vital role in cell physiology, including adaptation to metabolic stress, removal of dangerous substances, renewal during differentiation and development, and prevention of genome damage ( Levine and Kroemer, 2008 ; Levine and Kroemer, 2019 ).…”

Section: Instructionmentioning

confidence: 99%

Identification of a Novel Defined Immune-Autophagy-Related Gene Signature Associated With Clinical and Prognostic Features of Kidney Renal Clear Cell Carcinoma

Zhang¹,

Zhang²,

Sun³

et al. 2021

Front. Mol. Biosci.

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Background: As a common cancer of the urinary system in adults, renal clear cell carcinoma is metastatic in 30% of patients, and 1–2 years after diagnosis, 60% of patients die. At present, the rapid development of tumor immunology and autophagy had brought new directions to the treatment of renal cancer. Therefore, it was extremely urgent to find potential targets and prognostic biomarkers for immunotherapy combined with autophagy.Methods: Through GSE168845, immune-related genes, autophagy-related genes, and immune-autophagy-related differentially expressed genes (IAR-DEGs) were identified. Independent prognostic value of IAR-DEGs was determined by differential expression analysis, prognostic analysis, and univariate and multivariate Cox regression analyses. Then, the lasso Cox regression model was established to evaluate the correlation of IAR-DEGs with the immune score, immune checkpoint, iron death, methylation, and one-class logistic regression (OCLR) score.Results: In this study, it was found that CANX, BID, NAMPT, and BIRC5 were immune-autophagy-related genes with independent prognostic value, and the risk prognostic model based on them was well constructed. Further analysis showed that CANX, BID, NAMPT, and BIRC5 were significantly correlated with the immune score, immune checkpoint, iron death, methylation, and OCLR score. Further experimental results were consistent with the bioinformatics analysis.Conclusion: CANX, BID, NAMPT, and BIRC5 were potential targets and effective prognostic biomarkers for immunotherapy combined with autophagy in kidney renal clear cell carcinoma.

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Systematic profiling of ferroptosis gene signatures predicts prognostic factors in esophageal squamous cell carcinoma

Cited by 49 publications

References 41 publications

Esophageal Cancer Stem-like Cells Resist Ferroptosis-Induced Cell Death by Active Hsp27-GPX4 Pathway

Esophageal Cancer Stem-like Cells Resist Ferroptosis-Induced Cell Death by Active Hsp27-GPX4 Pathway

Immunological and prognostic significance of novel ferroptosis-related genes in soft tissue sarcoma

Identification of a Novel Defined Immune-Autophagy-Related Gene Signature Associated With Clinical and Prognostic Features of Kidney Renal Clear Cell Carcinoma

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