A Prognostic Ferroptosis-Related lncRNAs Signature Associated With Immune Landscape and Radiotherapy Response in Glioma

Zheng, Jianglin; Zhou, Zhongqiang; Qiu, Yue; Wang, Minjie; Yu, Hao; Wu, Zhipeng; Wang, Xuan; Jiang, Xueshi

doi:10.3389/fcell.2021.675555

Cited by 56 publications

(54 citation statements)

References 51 publications

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“…Upregulation of SNHG18 promotes resistance to radiotherapy in glioma by repressing Semaphorin 5A (Zheng et al, 2016). High expressions of PVT1 and SNHG18 in glioblastoma samples as opposed to LGG was validated in the previous study (Zheng et al, 2021). Notably, the role of lncRNAs APCDD1L-AS1, LINC00205, LINC00484, LINC00601, LINC00664, and LINC00886 was first reported and validated in the present study.…”

Section: Discussionsupporting

confidence: 70%

A Novel lncRNA Panel Related to Ferroptosis, Tumor Progression, and Microenvironment is a Robust Prognostic Indicator for Glioma Patients

Tian

et al. 2021

Front. Cell Dev. Biol.

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Objective: To establish a lncRNA panel related to ferroptosis, tumor progression, and microenvironment for prognostic estimation in patients with glioma.Methods: LncRNAs associated with tumor progression and microenvironment were screened via the weighted gene co-expression network analysis (WGCNA). Overlapped lncRNAs highlighted in WGCNA, related to ferroptosis, and incorporated in Chinese Glioma Genome Atlas (CGGA) were identified as hub lncRNAs. With expression profiles of the hub lncRNA, we conducted the least absolute shrinkage and selection operator (LASSO) regression and built a ferroptosis-related lncRNA signature to separate glioma patients with distinct survival outcomes. The lncRNA signature was validated in TCGA, the CGGA_693, and CGGA_325 cohorts using Kaplan-Meier survival analysis and ROC curves. The ferroptosis-related lncRNA panel was validated with 15 glioma samples using quantitative real-time PCR (qRT-PCR). Multivariate Cox regression was performed, and a nomogram was mapped and validated. Immune infiltration correlated to the signature was explored using TIMER and CIBERSORT algorithms.Results: The present study identified 30 hub lncRNAs related to ferroptosis, tumor progression, and microenvironment. With the 30 hub lncRNAs, we developed a lncRNA signature with distinct stratification of survival chance in patients with glioma in two independent cohorts (HRs>1, p < 0.05). The lncRNA signature revealed a panel of 14 lncRNAs, i.e., APCDD1L-AS1, H19, LINC00205, LINC00346, LINC00475, LINC00484, LINC00601, LINC00664, LINC00886, LUCAT1, MIR155HG, NEAT1, PVT1, and SNHG18. These lncRNA expressions were validated in clinical specimens using qRT-PCR. Robust predictive accuracies of the signature were present across different datasets at multiple timepoints. With univariate and multivariate regressions, we demonstrated that the risk score based on the lncRNA signature is an independent prognostic indicator after clinical factors were adjusted. A nomogram was constructed with these prognostic factors, and it has demonstrated decent classification and accuracy. Additionally, the signature-based classification was observed to be correlated with multiple clinical characteristics and molecular subtypes. Further, extensive immune cells were upregulated in the high-risk group, such as CD8+ T cell, neutrophil, macrophage, and myeloid dendritic cell, indicating increased immune infiltrations.Conclusion: We established a novel ferroptosis-related lncRNA signature that could effectively stratify the prognosis of glioma patients with adequate predictive performance.

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Section: Discussionsupporting

confidence: 70%

A Novel lncRNA Panel Related to Ferroptosis, Tumor Progression, and Microenvironment is a Robust Prognostic Indicator for Glioma Patients

Tian

et al. 2021

Front. Cell Dev. Biol.

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“…cell carcinoma, it has not been elucidated in EC. [27][28][29] As presented in the bubble diagram, the prognostic signature was positively correlated with memory CD4 + T cells, M2 macrophages, Tregs, and Tfh cells, whereas cancerassociated fibroblasts (CAFs) and NK cells were negatively correlated with it (Figure 7A, Table S4). Differential analysis of immune cells reported that compared with the low-risk group, plasma cells, endothelial cells, Tfh cells, and Tregs were upregulated in the high-risk group, whereas downregulated immune cells in the high-risk group included CAFs and NK cells (Figure 7B-G).…”

Section: Immune Landscape In Prognostic Signaturementioning

confidence: 93%

“…25,26 Prognostic signatures based on the absolute gene expression level of ferroptosisrelated lncRNAs (falncRNAs) have been recently defined for other solid tumors. [27][28][29] Remarkably, studies on the relationship between EC and falncRNAs are particularly scarce, which still needs to be further elucidated. Accordingly, the identification of falncRNAs to predict the prognosis and immune landscape and immunotherapy response of EC is helpful for the individualized treatment of patients.…”

Section: Introductionmentioning

confidence: 99%

A Promising Esophageal Cancer Prognostic Signature of Ferroptosis-Related LncRNA to Predict Immune Scenery and Immunotherapy Response

Liu¹,

Shi²,

Wei³

et al. 2021

IJGM

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Purpose Ferroptosis and long non-coding RNA (lncRNA) expression signatures have been associated with the clinical progression and immune-contexture of different solid tumors. The study aimed to identify a prognostic signature of ferroptosis-related lncRNAs (falncRNAs) to forecast the immune scenery and immunotherapy response in esophageal cancer (EC). Patients and Methods Gene expression profiles of EC were extracted from The Cancer Genome Atlas (TCGA) database, and ferroptosis-related genes were downloaded from the FerrDb database, which identified differentially expressed falncRNAs (DEfalncRNAs) via differential analysis. DEfalncRNA pairs associated with prognosis were identified by constructing a matrix, univariate and least absolute shrinkage and selection operator (LASSO) analysis. The prognostic signature was constructed by multivariate analysis. We appraised the forecasting capability of prognostic signature in survival, clinicopathological features, immune landscape, efficacy of immunotherapy, and drug sensitivity. The potential molecular mechanism of signature was investigated by gene set enrichment analysis (GSEA). Results We obtained 18 DEfalncRNA pairs to define a novel prognostic signature that was determined on a discovery cohort of 158 tumor samples and 11 adjacent normal tissues from TCGA and internally validated, with the definition of high- vs low-risk groups based on 3 years overall survival. We demonstrated that the high- vs low-risk groups differed for clinical parameters and computationally predicted drug sensitivity and tumor immune contexture, with the high-risk group having worse survival, more aggressive disease (node involvement, metastasis), reduced drug sensitivity, higher tumor mutation load, and gene signatures of infiltration of pro-tumoral immune cell subsets. The GSEA results revealed that ferroptosis and immunoregulatory pathways were significantly enriched in the high-risk group. Conclusion The prognostic signature based on falncRNAs has the potential to forecast the survival, immune scenery, efficacy of immunotherapy, and drug sensitivity of EC, which is helpful for clinical prediction and individualized treatment.

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“…These genesignatures constitute a risk-model, predicting the overall survival of the patients. To avoid overfitting, the models were each constructed in one database, e. g. Chinese Glioma Gene Atlas (CGGA), and validated using other databases, e. g. Repository for Molecular Brain in Neoplasia Data (REMBRANDT) or The Cancer Genome Atlas (TCGA) (26)(27)(28)(29)(30)(31)(32). The risk-models are shown and described in Table 1.…”

Section: Ferroptosis-gene Signatures In Gliomamentioning

confidence: 99%

Genetic Profiles of Ferroptosis in Malignant Brain Tumors and Off-Target Effects of Ferroptosis Induction

Dahlmanns

Yakubov

Dahlmanns³

2021

Front. Oncol.

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Glioblastoma represents the most devastating form of human brain cancer, associated with a very poor survival rate of patients. Unfortunately, treatment options are currently limited and the gold standard pharmacological treatment with the chemotherapeutic drug temozolomide only slightly increases the survival rate. Experimental studies have shown that the efficiency of temozolomide can be improved by inducing ferroptosis – a recently discovered form of cell death, which is different from apoptosis, necrosis, or necroptosis and, which is characterized by lipid peroxidation and reactive oxygen species accumulation. Ferroptosis can also be activated to improve treatment of malignant stages of neuroblastoma, meningioma, and glioma. Due to their role in cancer treatment, ferroptosis-gene signatures have recently been evaluated for their ability to predict survival of patients. Despite positive effects during chemotherapy, the drugs used to induce ferroptosis – such as erastin and sorafenib – as well as genetic manipulation of key players in ferroptosis – such as the cystine-glutamate exchanger xCT and the glutathione peroxidase GPx4 – also impact neuronal function and cognitive capabilities. In this review, we give an update on ferroptosis in different brain tumors and summarize the impact of ferroptosis on healthy tissues.

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A Prognostic Ferroptosis-Related lncRNAs Signature Associated With Immune Landscape and Radiotherapy Response in Glioma

Cited by 56 publications

References 51 publications

A Novel lncRNA Panel Related to Ferroptosis, Tumor Progression, and Microenvironment is a Robust Prognostic Indicator for Glioma Patients

A Novel lncRNA Panel Related to Ferroptosis, Tumor Progression, and Microenvironment is a Robust Prognostic Indicator for Glioma Patients

A Promising Esophageal Cancer Prognostic Signature of Ferroptosis-Related LncRNA to Predict Immune Scenery and Immunotherapy Response

Genetic Profiles of Ferroptosis in Malignant Brain Tumors and Off-Target Effects of Ferroptosis Induction

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