Ferroptosis-Related Gene-Based Prognostic Model and Immune Infiltration in Clear Cell Renal Cell Carcinoma

Zhao, Guojiang; Wu, Zonglong; Ge, Liyuan; Yang, Feilong; Hong, Kai; Zhang, Shudong; Ma, Lulin

doi:10.3389/fgene.2021.650416

Cited by 16 publications

(19 citation statements)

References 58 publications

(78 reference statements)

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“…According to our results, high methylation score is associated with high methylation of cg15044146 in ACACA, which results in resistance to ferroptosis and poor prognosis. This is inconsistent with previous studies (33,34). ZEB1 is an epithelial-mesenchymal transition (EMT) regulator as well as a lipogenic factor, could suppress GPX4 depletion- induced ferroptosis (35).…”

Section: Discussioncontrasting

confidence: 83%

A multiomic ferroptosis-associated prognostic signature incorporating epigenetic and transcriptional biomarkers for hepatocellular carcinoma

Chen¹,

Zhu²,

Chen³

et al. 2022

Transl Cancer Res TCR

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Background: Ferroptosis was reported to have tremendous promise in the treatment and prognosis of hepatocellular carcinoma (HCC). Here, we identified a novel ferroptosis-related prognostic signature incorporating epigenetic and transcriptional biomarkers could help predicting survival of patients with HCC.Methods: We employed multi-omics and clinical data from The Cancer Genome Atlas (TCGA) database to identify the ferroptosis-associated methylation CpG sites associated with HCC survival using sure independence screening (SIS). Then we utilized Kaplan-Meier curves to evaluate the prognostic significance of gene expression and DNA methylation. Receiver operating characteristic (ROC) curve was used predicting the 3-and 5-year survival. Mediation analysis of ferroptosis-related methylation and transcriptional score was performed.Results: We firstly identified 114 significant CpG sites under the criteria of false discovery rate (FDR) <0.05 in training set. Then we screened out 5 candidate CpG sites in validation set for multivariate screening and stepwise regression. We found that the high-risk group had significantly shorter survival time than the low-risk group in the prognostic signature combined with epigenetic and transcriptional scores (HR =2.72 95% CI: 2.01-3.68, P=8. 75E-11). And the predictive model involving clinical information, gene expression, and methylation data performed best for 3-year survival prediction (AUC =0.672) and 5-year survival prediction (AUC =0.742).Conclusions: Our results suggested a signature combining clinical information, ferroptosis-related gene expression, and methylation presented a superior ability for prognostic prediction in HCC, which may bring us novel tool and targets in the treatment of HCC.

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Section: Discussioncontrasting

confidence: 83%

A multiomic ferroptosis-associated prognostic signature incorporating epigenetic and transcriptional biomarkers for hepatocellular carcinoma

Chen¹,

Zhu²,

Chen³

et al. 2022

Transl Cancer Res TCR

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“…In addition, we constructed a scoring system to quantify the ferroptosis pattern of each CCs patient, defined as FS, to guide individualized prognostic analysis and precise treatment of CC. Studies have shown that an FRG-based prognostic nomogram could improve the estimation of the survival rate of patients with clear cell renal cell carcinoma ( 50 ). Similarly, a novel ferroptosis risk signature could be useful in predicting prognosis and reflecting immune infiltration in adrenocortical carcinoma ( 51 ).…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation in a Novel Quantification System of Ferroptosis Patterns for the Prediction of Prognosis and Immunotherapy Response in Left- and Right-Sided Colon Cancer

Zhang

Deng

et al. 2022

Front. Immunol.

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BackgroundThis study aimed to establish a novel quantification system of ferroptosis patterns and comprehensively analyze the relationship between ferroptosis score (FS) and the immune cell infiltration (ICI) characterization, tumor mutation burden (TMB), prognosis, and therapeutic sensitivity in left-sided and right-sided colon cancers (LCCs and RCCs, respectively).MethodsWe comprehensively evaluated the ferroptosis patterns in 444 LCCs and RCCs based on 59 ferroptosis-related genes (FRGs). The FS was constructed to quantify ferroptosis patterns by using principal component analysis algorithms. Next, the prognostic value and therapeutic sensitivities were evaluated using multiple methods. Finally, we performed weighted gene co-expression network analysis (WGCNA) to identify the key FRGs. The IMvigor210 cohort, TCGA-COAD proteomics cohort, and Immunophenoscores were used to verify the predictive abilities of FS and the key FRGs.ResultsTwo ferroptosis clusters were determined. Ferroptosis cluster B demonstrated a high degree of congenital ICI and stromal-related signal enrichment with a poor prognosis. The prognosis, response of targeted inhibitors, and immunotherapy were significantly different between high and low FS groups (HSG and LSG, respectively). HSG was characterized by high TMB and microsatellite instability-high subtype with poor prognosis. Meanwhile, LSG was more likely to benefit from immunotherapy. ALOX5 was identified as a key FRG based on FS. Patients with high protein levels of ALOX5 had poorer prognoses.ConclusionThis work revealed that the evaluation of ferroptosis subtypes will contribute to gaining insight into the heterogeneity in LCCs and RCCs. The quantification for ferroptosis patterns played a non-negligible role in predicting ICI characterization, prognosis, and individualized immunotherapy strategies.

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“…Conversely, it may release some immunogenic substances to activate the immune system and thus inhibit tumor growth [ 41 ]. Mast cells can enhance T cell-mediated immune responses, and the number of mast cells in the TME has been reported to correlate with reduced cancer progression and improved survival [ 42 ]. Dendritic cells are heterogeneous, intrinsic immune cells that can infiltrate and process tumors and play a key role in triggering antitumor T-cell immunity by providing tumor-derived antigens to naive T cells, and are major therapeutic targets for tumor immunotherapy [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Ferroptosis-Related Genes Are Potential Therapeutic Targets and the Model of These Genes Influences Overall Survival of NSCLC Patients

Zhang

et al. 2022

Cells

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Background: Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSCC) are two of the most common subtypes of non-small cell lung cancer (NSCLC), with high mortality rates and rising incidence worldwide. Ferroptosis is a mode of programmed cell death caused by lipid peroxidation, the accumulation of reactive oxygen species, and is dependent on iron. The recent discovery of ferroptosis has provided new insights into tumor development, and the clinical relevance of ferroptosis for tumor therapy is being increasingly appreciated. However, its role in NSCLC remains to be explored. Methods: The clinical and molecular data for 1727 LUAD and LUSCC patients and 73 control individuals were obtained from the Gene Expression Omnibus (GEO) database and the Cancer Genome Atlas (TCGA) database. Gene expression profiles, copy number variations and somatic mutations of 57 ferroptosis-related genes in 1727 tumor samples from the four datasets were used in a univariate Cox analysis and consensus clustering analysis. The biological signatures of each pattern were identified. A ferroptosis score was generated by combining the univariate Cox regression analysis and random forest algorithm followed by principal component analysis (PCA) and further investigated for its predictive and therapeutic value in LUAD and LUSCC. Results: The expression of 57 ferroptosis-related genes in NSCLC patients differed significantly from that of normal subjects. Based on unsupervised clustering of ferroptosis-related genes, we divided all patients into three ferroptosis expression pattern groups, which showed differences in ferroptosis-associated gene expression patterns, immune cell infiltration levels, prognostic characteristics and enriched pathways. Using the differentially expressed genes in the three ferroptosis expression patterns, a set of 17 ferroptosis-related gene prognostic models was established, which clustered all patients in the cohort into a low score group and a high score group, with marked differences in prognosis (p < 0.001). The high ferroptosis score was significantly associated with positive response to radiotherapy (p < 0.001), high T stage (p < 0.001), high N stage (p < 0.001) and high-grade tumor (p < 0.001) characteristics. Conclusions: The 17 ferroptosis-associated genes show great potential for stratifying LUAD and LUSCC patients into high and low risk groups. Interestingly, a high ferroptosis score in LUAD patients was associated with a good prognosis, whereas a similar high ferroptosis score in LUSCC patients was associated with a poor prognosis. Familiarity with the mechanisms underlying ferroptosis and its implications for the treatment of NSCLC, as well as its effect on OS and PFS, may provide guidance and insights in developing new therapeutic targets for NSCLC.

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Ferroptosis-Related Gene-Based Prognostic Model and Immune Infiltration in Clear Cell Renal Cell Carcinoma

Cited by 16 publications

References 58 publications

A multiomic ferroptosis-associated prognostic signature incorporating epigenetic and transcriptional biomarkers for hepatocellular carcinoma

A multiomic ferroptosis-associated prognostic signature incorporating epigenetic and transcriptional biomarkers for hepatocellular carcinoma

Identification and Validation in a Novel Quantification System of Ferroptosis Patterns for the Prediction of Prognosis and Immunotherapy Response in Left- and Right-Sided Colon Cancer

Ferroptosis-Related Genes Are Potential Therapeutic Targets and the Model of These Genes Influences Overall Survival of NSCLC Patients

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