Ferroptosis Patterns and Tumor Microenvironment Infiltration Characterization in Bladder Cancer

Xia, Qi‐Dong; Sun, Jian‐Xuan; Liu, Chen‐Qian; Xu, Jin‐Zhou; An, Ye; Xu, Meng‐Yao; Liu, Zheng; Hu, Jia; Wang, Shaogang

doi:10.3389/fcell.2022.832892

Cited by 18 publications

(14 citation statements)

References 35 publications

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“…DEGs among the three LUAD subtypes were screened using the R package “limma” following p.adj < 0.001 and then combined and visualized on a Venn diagram using the package “VennDiagram.” Detailed information of DEGs is presented in Supplementary Table S2 . Packages “clusterProfiler,” “org.Hs.eg.db,” “enrichplot,” and “ggplot2” were applied to explore the potential biological functions and signaling pathways of the DEGs ( Xia et al, 2022b ).…”

Section: Methodsmentioning

confidence: 99%

m7G-Associated subtypes, tumor microenvironment, and validation of prognostic signature in lung adenocarcinoma

Wang

Zhao

et al. 2022

Front. Genet.

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Background: 7-Methylguanosine (m7G) is an important posttranscriptional modification that regulates gene expression and is involved in tumorigenesis and development. Tumor microenvironment has been proven to be highly involved in tumor progression and prognosis. However, how m7G-associated genes affect the tumor microenvironment of patients with lung adenocarcinoma (LUAD) remains to be further clarified.Methods: The genetic alterations of m7G-associated genes and their associations with the prognosis and tumor microenvironment in LUAD patients were systemically analyzed. An m7G-Riskscore was established and analyzed for its performance in disease prognosis and association with patient response to immunotherapy. Expression of the model genes at the protein level was investigated through ex vivo experiments. A nomogram was finally obtained based on the m7G-Riskscore and several significant clinical pathological features.Results: m7G-Associated genes were obtained from five LUAD datasets from The Cancer Genome Atlas and Gene Expression Omnibus databases, and their expression pattern was determined. Based on the m7G-associated genes, three LUAD clusters were defined. The differentially expressed genes from the three clusters were screened and used to further divide the LUAD patients into two gene clusters. It was demonstrated that the alterations of m7G-associated genes were associated with the clinical pathological features, prognosis, and tumor immune infiltration in LUAD patients. An m7G-Riskscore including CAND1, RRM2, and SLC2A1 was obtained with robust and accurate prognostic performance. WB and cell immunofluorescence also showed significant dysregulation of CAND1, RRM2, and SLC2A1 in LUAD. In addition, a nomogram was established to improve the clinical feasibility of the m7G-Riskscore. Correlation analysis revealed that patients with a lower m7G-Riskscore had higher immune and stromal scores, responded well to chemotherapeutics and multiple targeted drugs, and survived longer. Patients with a higher m7G-Riskscore tended to suffer from a higher tumor mutation burden. Furthermore, the m7G-Riskscore exhibited significant associations with immune cell infiltration and cancer stemness.Conclusion: This study systemically analyzed m7G-associated genes and identified their potential role in tumor microenvironment and prognosis in patients with LUAD. The findings of the present study may help better understand LUAD from the m7G perspective and also provide a new thought toward the prognosis and treatment of LUAD.

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Section: Methodsmentioning

confidence: 99%

m7G-Associated subtypes, tumor microenvironment, and validation of prognostic signature in lung adenocarcinoma

Wang

Zhao

et al. 2022

Front. Genet.

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“…Another SUMOylation pattern could predict the prognosis and tumor microenvironment infiltration characterization in bladder cancer ( Xia et al, 2022b ). Moreover, Qi-Dong et al developed a ferroptosis pattern in bladder cancer that could guide the clinical therapeutic strategy ( Xia et al, 2022c ).…”

Section: Discussionmentioning

confidence: 99%

Identification and verification of the pyroptosis-related prognostic signature and its associated regulatory axis in bladder cancer

Ding

Mao

2022

Front. Cell Dev. Biol.

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Background: Pyroptosis is an inflammatory form of cell death triggered by certain inflammasomes. Accumulating studies have shown the involvement of pyroptosis in the proliferation, invasion, and metastasis and prognosis of cancer. The prognostic value of pyroptosis-related genes (PRGs) and their association with immune infiltration in bladder cancer have not yet been elucidated.Methods: We performed a comprehensive analysis of the prognostic value and immune infiltrates of PRGs in bladder cancer using the TCGA dataset. qRT-PCR was also performed to verify our result.Results: Among 33 PRGs, 14 PRGs were upregulated or downregulated in bladder cancer tissue versus normal tissue. We also summarized copy number variations and somatic mutations of PRGs in bladder cancer. By using consensus clustering analysis of PRGs with prognostic significance, we divided the bladder cancer cohort into two subtypes significantly by different prognosis and immune infiltration. Using the LASSO Cox regression analysis, a prognostic signature including six PRGs was constructed for bladder cancer and the patients could be classified into a low- or high-risk group. Interestingly, this prognostic signature had a favorable performance for predicting the prognosis of bladder cancer patients. Moreover, further analysis demonstrated a significant difference in gender, tumor grade, clinical stage, TNM stage, immunoScore, and immune cell infiltration between the high- and low-risk groups in bladder cancer. We also identified an lncRNA SNHG14/miR-20a-5p/CASP8 regulatory axis in bladder cancer by constructing a ceRNA network.Conclusion: We identified a PRG-associated prognostic signature associated with the prognosis and immune infiltrates for bladder cancer and targeting pyroptosis may be an alternative approach for therapy. Further vivo and vitro experiments are necessary to verify these results.

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“…A total of 232 ARGs were obtained from the Human Autophagy Database (available online: ). One hundred twenty-one ferroptosis-verified driver genes were obtained from the FerrDb database (available online: ), as described previously ( 21 ).…”

Section: Methodsmentioning

confidence: 99%

“…One hundred twenty-one ferroptosis-verified driver genes were obtained from the FerrDb database (available online: http://www.datjar. com:40013/bt2104/), as described previously (21).…”

Section: Data Sourcesmentioning

confidence: 99%

Autophagy-related prognostic signature characterizes tumor microenvironment and predicts response to ferroptosis in gastric cancer

et al. 2022

Front. Oncol.

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BackgroundGastric cancer (GC) is an important disease and the fifth most common malignancy worldwide. Autophagy is an important process for the turnover of intracellular substances. Autophagy-related genes (ARGs) are crucial in cancer. Accumulating evidence indicates the clinicopathological significance of the tumor microenvironment (TME) in predicting prognosis and treatment efficacy.MethodsClinical and gene expression data of GC were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. A total of 22 genes with differences in expression and prognosis were screened from 232 ARGs. Three autophagy patterns were identified using an unsupervised clustering algorithm and scored using principal component analysis to predict the value of autophagy in the prognosis of GC patients. Finally, the relationship between autophagy and ferroptosis was validated in gastric cancer cells.ResultsThe expression of ARGs showed obvious heterogeneity in GC patients. Three autophagy patterns were identified and used to predict the overall survival of GC patients. These three patterns were well-matched with the immunophenotype. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses showed that the biological functions of the three autophagy patterns were different. A scoring system was then set up to quantify the autophagy model and further evaluate the response of the patients to the immunotherapy. Patients with high autophagy scores had a more severe tumor mutation burden and better prognosis. High autophagy scores were accompanied by high microsatellite instability. Patients with high autophagy scores had significantly higher PD-L1 expression and increased survival. The experimental results confirmed that the expression of ferroptosis genes was positively correlated with the expression of autophagy genes in different autophagy clusters, and inhibition of autophagy dramatically reversed the decrease in ferroptotic cell death and lipid accumulation.ConclusionsAutophagy patterns are involved in TME diversity and complexity. Autophagy score can be used as an independent prognostic biomarker in GC patients and to predict the effect of immunotherapy and ferroptosis-based therapy. This might benefit individualized treatment for GC.

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Ferroptosis Patterns and Tumor Microenvironment Infiltration Characterization in Bladder Cancer

Cited by 18 publications

References 35 publications

m7G-Associated subtypes, tumor microenvironment, and validation of prognostic signature in lung adenocarcinoma

m7G-Associated subtypes, tumor microenvironment, and validation of prognostic signature in lung adenocarcinoma

Identification and verification of the pyroptosis-related prognostic signature and its associated regulatory axis in bladder cancer

Autophagy-related prognostic signature characterizes tumor microenvironment and predicts response to ferroptosis in gastric cancer

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