A New Prognostic Risk Signature of Eight Ferroptosis-Related Genes in the Clear Cell Renal Cell Carcinoma

Chen, Ji; Zhan, Yating; Zhang, Rongrong; Chen, Bin; Huang, Junting; Li, Chunxue; Zhang, Wenjie; Wang, Yajing; Gao, Yuxiang; Zheng, Jianjian; Li, Yeping

doi:10.3389/fonc.2021.700084

Cited by 10 publications

(8 citation statements)

References 40 publications

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“…Altogether, our findings have profound implications for experimental and clinical immunotherapy since some cancer treatments, such as radiotherapy, result in mixtures of cell death 41 , 74 , 75 . Our data possibly explain the notion that the ferroptosis correlates with poor prognosis of patients suffering from esophageal 76 , gastric 77 and renal 78 carcinoma. Finally, our results advance a concept in which immunogenic cell death is not merely the result of exposure to CRT at the plasma membrane and the release of intracellular contents such as DAMP or cytokines 63 .…”

Section: Discussionsupporting

confidence: 71%

Cancer cells dying from ferroptosis impede dendritic cell-mediated anti-tumor immunity

et al. 2022

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Immunogenic cell death significantly contributes to the success of anti-cancer therapies, but immunogenicity of different cell death modalities widely varies. Ferroptosis, a form of cell death that is characterized by iron accumulation and lipid peroxidation, has not yet been fully evaluated from this perspective. Here we present an inducible model of ferroptosis, distinguishing three phases in the process—‘initial’ associated with lipid peroxidation, ‘intermediate’ correlated with ATP release and ‘terminal’ recognized by HMGB1 release and loss of plasma membrane integrity—that serves as tool to study immune cell responses to ferroptotic cancer cells. Co-culturing ferroptotic cancer cells with dendritic cells (DC), reveals that ‘initial’ ferroptotic cells decrease maturation of DC, are poorly engulfed, and dampen antigen cross-presentation. DC loaded with ferroptotic, in contrast to necroptotic, cancer cells fail to protect against tumor growth. Adding ferroptotic cancer cells to immunogenic apoptotic cells dramatically reduces their prophylactic vaccination potential. Our study thus shows that ferroptosis negatively impacts antigen presenting cells and hence the adaptive immune response, which might hinder therapeutic applications of ferroptosis induction.

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Section: Discussionsupporting

confidence: 71%

Cancer cells dying from ferroptosis impede dendritic cell-mediated anti-tumor immunity

et al. 2022

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“…Based on the five databases, a signature including nine genes was employed to predict outcomes of ccRCC patients. Except MT1G and CA9, the other seven genes of the signature were not involved in previous signatures [16,18,19,46,[49][50][51], which might be attributed to using a fragmentary gene set. Therefore, the nine-gene signature in this study could be more successful at distinguishing high-risk and low-risk patients and more accurate in predicting the prognosis of patients.…”

Section: Discussionmentioning

confidence: 87%

Identification and Validation of a Novel Ferroptotic Prognostic Genes-Based Signature of Clear Cell Renal Cell Carcinoma

Shi

Zheng

Liang

et al. 2022

Cancers

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Renal cell carcinoma (RCC), as one of the primary urological malignant neoplasms, shows poor survival, and the leading pathological type of RCC is clear cell RCC (ccRCC). Differing from other cell deaths (such as apoptosis, necroptosis, pyroptosis, and autophagy), ferroptosis is characterized by iron-dependence, polyunsaturated fatty acid oxidization, and lipid peroxide accumulation. We analyzed the ferroptosis database (FerrDb V2), Gene Expression Omnibus database, The Cancer Genome Atlas database, and the ArrayExpress database. Nine genes that were differentially expressed and related to prognosis were involved in the ferroptotic prognostic model via the least absolute shrinkage and selection operator Cox regression analysis, which was established in ccRCC patients from the kidney renal clear cell carcinoma (KIRC) cohort in TCGA database, and validated in ccRCC patients from the E-MTAB-1980 cohort in the ArrayExpress database. The signature could be an independent prognostic factor for ccRCC, and high-risk patients showed worse overall survival. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were utilized to investigate the potential mechanisms. The nine genes in ccRCC cells with erastin or RSL3 treatment were validated to find the crucial gene. The glutaminase 2 (GLS2) gene was upregulated during ferroptosis in ccRCC cells, and cells with GLS2 shRNA displayed lower survival, a lower glutathione level, and a high lipid peroxide level, which illustrated that GLS2 might be a ferroptotic suppressor in ccRCC.

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“…Loss of TP53 prevents nuclear accumulation of DPP4 and thus facilitates plasma-membrane-associated DPP4-dependent lipid peroxidation, resulting in ferroptosis ( 26 ). CARS1 has been included in a novel prognostic signature by Chen et al., which effectively predicts the prognosis of Clear Cell Renal Cell Carcinoma ( 27 ). Activation of SAT1 induces lipid peroxidation and sensitizes cells to undergo ferroptosis upon reactive oxygen species (ROS)-induced stress ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

A novel 10-gene ferroptosis-related prognostic signature in acute myeloid leukemia

Zhu

Lang²,

Zhan³

et al. 2022

Front. Oncol.

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Acute myeloid leukemia (AML) is one of the most common hematopoietic malignancies and exhibits a high rate of relapse and unfavorable outcomes. Ferroptosis, a relatively recently described type of cell death, has been reported to be involved in cancer development. However, the prognostic value of ferroptosis-related genes (FRGs) in AML remains unclear. In this study, we found 54 differentially expressed ferroptosis-related genes (DEFRGs) between AML and normal marrow tissues. 18 of 54 DEFRGs were correlated with overall survival (OS) (P<0.05). Using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis, we selected 10 DEFRGs that were associated with OS to build a prognostic signature. Data from AML patients from the International Cancer Genome Consortium (ICGC) cohort as well as the First Affiliated Hospital of Wenzhou Medical University (FAHWMU) cohort were used for validation. Notably, the prognostic survival analyses of this signature passed with a significant margin, and the riskscore was identified as an independent prognostic marker using Cox regression analyses. Then we used a machine learning method (SHAP) to judge the importance of each feature in this 10-gene signature. Riskscore was shown to have the highest correlation with this 10-gene signature compared with each gene in this signature. Further studies showed that AML was significantly associated with immune cell infiltration. In addition, drug-sensitive analysis showed that 8 drugs may be beneficial for treatment of AML. Finally, the expressions of 10 genes in this signature were verified by real-time quantitative polymerase chain reaction. In conclusion, our study establishes a novel 10-gene prognostic risk signature based on ferroptosis-related genes for AML patients and FRGs may be novel therapeutic targets for AML.

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A New Prognostic Risk Signature of Eight Ferroptosis-Related Genes in the Clear Cell Renal Cell Carcinoma

Cited by 10 publications

References 40 publications

Cancer cells dying from ferroptosis impede dendritic cell-mediated anti-tumor immunity

Cancer cells dying from ferroptosis impede dendritic cell-mediated anti-tumor immunity

Identification and Validation of a Novel Ferroptotic Prognostic Genes-Based Signature of Clear Cell Renal Cell Carcinoma

A novel 10-gene ferroptosis-related prognostic signature in acute myeloid leukemia

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