Identification of a Novel PPAR Signature for Predicting Prognosis, Immune Microenvironment, and Chemotherapy Response in Bladder Cancer

Zhu, Ke; Deng, Wen; Deng, Hui; Liu, Xiaoqiang; Wang, Gongxian; Fu, Bin

doi:10.1155/2021/7056506

Cited by 5 publications

(4 citation statements)

References 47 publications

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“…Fatty acid desaturase 2 (FADS2) could fix in fatty acyl chain to adjust unsaturated fatty acids through the introduction of a double bond between carbon. Zhu et al confirmed that FADS2 was correlated with immune infiltration of tumor cells through participation in peroxisome proliferator-activated receptors (PPARs) signaling through GSEA enrichment analysis (Zhu et al, 2021). Furthermore, interference with FADS2 expression could protect immortalized primary hepatocytes and lung cancer cells from erastin-induced ferroptosis.…”

Section: Discussionmentioning

confidence: 95%

Identifification and validation of ferroptosis signatures and immune infifiltration characteristics associated with intervertebral disc degeneration

Zhang

Cui²,

Wang³

et al. 2023

Front. Genet.

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Ferroptosis and immune infiltration play an important role in the pathogenesis of intervertebral disc degeneration (IDD). However, there is still a lack of comprehensive analysis on the interaction between ferroptosis-related genes (FRGs) and immune microenvironment in IDD patients. Therefore, this study aims to explore the correlation between FRGs characteristics and immune infiltration in the progression of IDD. The expression profiles (GSE56081 and GSE70362) and FRGs were downloaded from the comprehensive gene expression omnibus (GEO) and FerrDb database, respectively, and the differences were analyzed using R. The intersection of IDD related differential genes (DEGs) and FRGs was taken as differentially expressed FRGs (DE-FRGs) and GO and KEGG enrichment analysis was conducted. Then, we used least absolute shrinkage and selection operator (LASSO) regression algorithm and support vector machine (SVM) algorithm to screen feature genes and draw ROC curve judge the diagnostic value of key DE-FRGs. Then CIBERSORT algorithm is used to evaluate the infiltration of immune cells and analyze the correlation between key DE-FRGs and immune infiltration. Based on the analysis results, we conducted single gene GSEA analysis on key DE-FRGs. RT-PCR and immunohistochemistry further verified the clinical value of the results of biochemical analysis and screening. Seven key DE-FRGs were screened, including the upregulated genes NOX4 and PIR, and the downregulated genes TIMM9, ATF3, ENPP2, FADS2 and TFAP2A. Single gene GSEA analysis further elucidates the role of DE-FRGs in IDD associated with ferroptosis. Correlation analysis showed that seven key DE-FRGs were closely related to immune infiltration in the development of IDD. Finally, RT-PCR and immunohistochemical staining showed that NOX4, ENPP2, FADS2 and TFAP2A were statistically significant differences. In this study, we explored the connection between ferroptosis related characteristics and immune infiltration in IDD, and confirmed that NOX4, ENPP2, FADS2, and TFAP2A may become biomarkers and potential therapeutic targets for IDD.

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Section: Discussionmentioning

confidence: 95%

Identifification and validation of ferroptosis signatures and immune infifiltration characteristics associated with intervertebral disc degeneration

Zhang

Cui²,

Wang³

et al. 2023

Front. Genet.

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“…Through the results of Gene Ontology and KEGG enrichment analysis, FADS2 plays an oncogenic driver role by driving cancer cells proliferation, cell migration, and EMT through VEGF, MAPK, and PPAR pathways. An analysis of GSEA by Zhu K et al revealed that the PPAR signature correlated with the infiltration of tumor immune cells [ 21 ]. In a recent study, Mokhtari et al showed a cross-talk between the unsaturated fatty acid synthesis pathway and arachidonic acid metabolism and that the PPAR signaling pathway was regulated via these pathways.…”

Section: Discussionmentioning

confidence: 99%

The role of fatty acid desaturase 2 in multiple tumor types revealed by bulk and single-cell transcriptomes

Chen

2023

Lipids Health Dis

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Background Previous studies have demonstrated the important role of fatty acid desaturase 2 (FADS2) in governing tumorigenesis and tumor metastasis. Although FADS2 is an essential regulator of fatty acid metabolism, its prognostic and immunotherapeutic value remains uncertain. Methods The role of FADS2 was investigated across different types of tumors. Besides, the relationship between FADS2 and survival prognosis, clinicopathologic features, tumor-infiltrating immune cells, immunoregulatory genes, chemokines, chemokines receptor, tumor mutational burden (TMB), and microsatellite instability (MSI) was also explored. FADS2-related genes enrichment analysis was performed to further explore the molecular function of FADS2. Finally, the relationship between FADS2 expression and altered functional states in single-cell levels across different tumor cells was explored. Results FADS2 was increased in most tumor tissues. Elevated FADS2 expression was associated with a poor overall survival (OS) and disease-free survival (DFS). FADS2 amplification was germane to worse progress-free survival (PFS). In addition, FADS2 correlated with the majority of tumor-infiltrating immune cells, immunoregulatory genes, and chemokines. Especially, FADS2 expression positively correlated with cancer-associated fibroblast (CAFs) infiltration. Gene Ontology and KEGG analysis demonstrated that FADS2 was involved in the fatty acid metabolic process, arachidonic acid metabolism, RAS, PPAR, and VEGF pathway. FADS2 had a positive relationship with tumor biological behaviors such as inflammation, cell cycle, proliferation, DNA damage, and DNA repair response in single-cell levels. Conclusions FADS2 can serve as a potential prognostic and immunotherapeutic biomarker for multiple tumors, revealing new insights and evidence for cancer treatment.

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“…The differential IC50 of chemotherapeutic agents between low and high FBN2 expression groups was predicted by the ‘pRRophetic’ package [ 35 ]. Based on gene expression microarray data, the pRRophetic package, which was used to determine IC50 with success in previous research [ 36 , 37 , 38 , 39 ], was performed for the prediction of clinical chemotherapeutic response by using statistical models from the gene expression and drug sensitivity data from cell lines in the Cancer Genome Project [ 40 ] as a training set.…”

Section: Methodsmentioning

confidence: 99%

A comprehensive analysis of FBN2 in bladder cancer: A risk factor and the tumour microenvironment influencer

Lai

et al. 2023

IET Systems Biology

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Bladder cancer (BLCA) is a common and difficult‐to‐manage disease worldwide. Most common type of BLCA is urothelial carcinoma (UC). Fibrillin 2 (FBN2) was first discovered while studying Marfan syndrome, and its encoded products are associated with elastin fibres. To date, the role of FBN2 in BLCA remains unclear. The authors first downloaded data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The patients were divided into high FBN2 expression and low FBN2 expression groups, and the survival curve, clinical characteristics, tumour microenvironment (TME), and immune cell differences were analysed between the two groups. Then, the differentially expressed genes (DEGs) were filtered, and functional enrichment for DEGs was performed. Finally, chemotherapy drug susceptibility analysis based on the high and low FBN2 groups was conducted. The authors found upregulated expression of FBN2 in BLCA and proved that FBN2 could be an independent prognostic factor for BLCA. TME analysis showed that the expression of FBN2 affects several aspects of the TME. The upregulated expression of FBN2 was associated with a high stromal score, which may lead to immunosuppression and be detrimental to immunotherapy. In addition, the authors found that NK cells resting, macrophage M0 infiltration, and other phenomena of immune cell infiltration appeared in the high expression group of FBN2. The high expression of FBN2 was related to the high sensitivity of some chemotherapy drugs. The authors systematically investigated the effects and mechanisms of FBN2 on BLCA and provided a new understanding of the role of FBN2 as a risk factor and TME influencer in BLCA.

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Identification of a Novel PPAR Signature for Predicting Prognosis, Immune Microenvironment, and Chemotherapy Response in Bladder Cancer

Cited by 5 publications

References 47 publications

Identifification and validation of ferroptosis signatures and immune infifiltration characteristics associated with intervertebral disc degeneration

Identifification and validation of ferroptosis signatures and immune infifiltration characteristics associated with intervertebral disc degeneration

The role of fatty acid desaturase 2 in multiple tumor types revealed by bulk and single-cell transcriptomes

A comprehensive analysis of FBN2 in bladder cancer: A risk factor and the tumour microenvironment influencer

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