Molecular Identification of Immunity- and Ferroptosis-related Gene Signature in Non-small Cell Lung Cancer

Liu, Taisheng; Zhang, Jinye; Hu, Xiaoshan; Xie, Tao; Zhang, Jiän

doi:10.21203/rs.3.rs-390478/v1

Cited by 3 publications

(2 citation statements)

References 25 publications

(25 reference statements)

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“…The dataset contains gene expression data from 433 patients with GC. 383 FRGs were derived from ferroptosis database (http://www.zhounan.org/ferrdb/) [18][19][20]. The "limma" package was used for integration and difference analysis between datasets [21].…”

Section: Methodsmentioning

confidence: 99%

Prognostic Model and Immune Infiltration of Ferroptosis Subcluster-Related Modular Genes in Gastric Cancer

Deng

Lin

Gan

et al. 2022

Journal of Oncology

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Background. Gastric cancer (GC) is one of the gastrointestinal tumors with the highest mortality rate. The number of GC patients is still high. As a way of iron-dependent programmed cell death, ferroptosis activates lipid peroxidation and accumulates large reactive oxygen species. The role of ferroptosis in GC prognosis was underrepresented. The objective was to investigate the role of ferroptosis-related genes (FRGs) in the prognosis and development of GC. Methods. Datasets of GC patients were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database that include clinical information and RNA seq data. Through nonnegative matrix factorization (NMF) clustering, we identified and unsupervised cluster analysis of the expression matrix of FRGs. And we constructed the co-expression network between genes and clinical characteristics by consensus weighted gene co-expression network analysis (WGCNA). The prognostic model was constructed by univariate and multivariate regression analysis. The potential mechanisms of development and prognosis in GC were explored by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, gene ontology (GO), tumor immune microenvironment (TIME), and tumor mutation burden (TMB). Results. Two molecular subclusters with different expression patterns of FRGs were identified, which have significantly different survival states. Ferroptosis subcluster-related modular genes were identified by WGCNA. Based on 8 ferroptosis subcluster-related modular genes (collagen triple helix repeat containing 1 (CTHRC1), podoplanin (PDPN), procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2), glutamine-fructose-6-phosphate transaminase 2 (GFPT2), ATP-binding cassette subfamily A member 1 (ABCA1), G protein-coupled receptor 176 (GPR176), serpin family E member 1 (SERPINE1), dual specificity phosphatase 1 (DUSP1)) and clinicopathological features, a nomogram was constructed and validated for their predictive efficiency on GC prognosis. Through receiver operating characteristic (ROC) analysis, the results showed that the area under the curve (AUC) of 1-, 3-, and 5-year survival were 0.721, 0.747, and 0.803, respectively, indicating that the risk-scoring model we constructed had good prognosis efficacy in GC. The degree of immune infiltration in high-risk group was largely higher than low-risk group. It indicated that the immune cells have a good response in high-risk group of GC. The TMB of high-risk group was higher, which could generate more mutations and was more conducive to the body’s resistance to the development of cancer. Conclusion. The risk-scoring model based on 8 ferroptosis subcluster-related modular genes has shown outstanding advantages in predicting patient prognosis. The interaction of ferroptosis in GC development may provide new insights into exploring molecular mechanisms and targeted therapies for GC patients.

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Section: Methodsmentioning

confidence: 99%

Prognostic Model and Immune Infiltration of Ferroptosis Subcluster-Related Modular Genes in Gastric Cancer

Deng

Lin

Gan

et al. 2022

Journal of Oncology

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“…In particular, TCGA database included the RNA-seq data as well as related clinical data of 306 CC patients and 3 normal specimens, the GTEx database included the RNAseq data of 78 normal samples, and the GEO dataset included RNA-seq and clinical data of 300 tumor specimens. 60 ferroptosis-related genes constructed by the risk model were retrieved from the previous research [20][21][22].…”

Section: Methodsmentioning

confidence: 99%

Systematic Construction and Validation of a Novel Ferroptosis-Related Gene Model for Predicting Prognosis in Cervical Cancer

Qin

Jiang

et al. 2022

Journal of Immunology Research

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Background and Purpose. Ferroptosis, a mechanism of cell death that is iron-dependent, participates in various pathologies of cancer (CC). Nevertheless, the specific function that ferroptosis plays in the onset and progression of cervical cancer (CC) is yet uncertain. This research sought to examine the value of ferroptosis-related genes (FRGs) in the progression and prognosis of CC. Methods. Datasets containing RNA sequencing and corresponding clinical data of cervical cancer patients were obtained from searching publicly accessible databases. The “NMF” R package was conducted to calculate the matrix of the screened prognosis gene expression. Ferroptosis-related differential genes in cervical cancer were detected using the “limma” R function and WGCNA. The least absolute shrinkage and selection operator (LASSO) algorithm and Cox regression analysis were conducted to develop a novel prognostic signature. The prediction model was verified by the nomogram integrating clinical characteristics; the GSE44001 dataset was used as an external verification. Then, the immune status and tumor mutation load were explored. Finally, immunohistochemistry as well as quantitative polymerase chain reaction (RT-qPCR) was utilized to ascertain the expression of FRGs. Results. Two molecular subgroups (cluster 1 and cluster 2) with different FRG expression patterns were recognized. A ferroptosis-related model based on 4 genes (VEGFA, CA9, DERL3, and RNF130) was developed through TCGA database to identify the unfavorable prognosis cases. Patients in cluster 1 showed significantly decreased overall survival in contrast with those in cluster 2 ( P < 0.05 ). The LASSO technique and Cox regression analysis were both utilized to establish the independence of the prognostic model. The validity of nomogram prognostic predictions has been well demonstrated for 3- and 5-year survival in both internal and external data validation cohorts. These two subgroups showed striking differences in tumor-infiltrating leukocytes and tumor mutation burden. The low-risk subgroup showed a longer overall survival time with a higher immune cell score and higher tumor mutation rate. Gene functional enrichment analyses revealed predominant enrichment in various tumor-associated signaling pathways. Finally, the expression of each gene was confirmed by immunohistochemistry and RT-qPCR. Conclusion. A novel and comprehensive ferroptosis-related gene model was proposed for cervical cancer which was capable of distinguishing the patients independently with high risk for poor survival, and targeting ferroptosis may represent a promising approach for the treatment of CC.

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The role of ferroptosis in lung cancer

Zhu

Tang

et al. 2021

Biomark Res

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Lung cancer is one of the most common cancers in the world. Although medical treatment has made impressive progress in recent years, it is still one of the leading causes of cancer-related deaths in men and women. Ferroptosis is a type of non-apoptotic cell death modality, usually characterized by iron-dependent lipid peroxidation, rather than caspase-induced protein cleavage. Excessive or lack of ferroptosis is associated with a variety of diseases, including cancer and ischaemia-reperfusion injury. Recent preclinical evidence suggests that targeting ferroptotic pathway is a potential strategy for the treatment of lung cancer. In this review, we summarize the core mechanism and regulatory network of ferroptosis in lung cancer cells, and highlight ferroptosis induction-related tumor therapies. The reviewed information may provide new insights for targeted lung cancer therapy.

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Molecular Identification of Immunity- and Ferroptosis-related Gene Signature in Non-small Cell Lung Cancer

Cited by 3 publications

References 25 publications

Prognostic Model and Immune Infiltration of Ferroptosis Subcluster-Related Modular Genes in Gastric Cancer

Prognostic Model and Immune Infiltration of Ferroptosis Subcluster-Related Modular Genes in Gastric Cancer

Systematic Construction and Validation of a Novel Ferroptosis-Related Gene Model for Predicting Prognosis in Cervical Cancer

The role of ferroptosis in lung cancer

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