SUMOylation Pattern Predicts Prognosis and Indicates Tumor Microenvironment Infiltration Characterization in Bladder Cancer

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

doi:10.3389/fimmu.2022.864156

Cited by 15 publications

(15 citation statements)

References 56 publications

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“…In the meantime, four LUAD datasets, GSE13213, GSE31210, GSE68465, and GSE30219, were obtained from the Gene Expression Omnibus (GEO) database ( https://www.ncbi.nlm.nih.gov/geo/ ). Data from the five datasets were combined and normalized using the R software to eliminate potential batch effects ( Xia et al, 2022a ). Corresponding clinical data were also extracted, and samples with missing data of OS or exhibiting OS as 0 were excluded.…”

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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“…Machine learning-based unsupervised consensus was used to cluster 398 COAD patients in the TCGA cohort to explore the relationship between m7G-related DELs and COAD subtypes ( 16 , 18 ). By increasing the clustering variable (k) from 2 to 9, we found that when k =2, the within-group correlation was highest, whereas the between-group correlation was low ( Figure 2A ).…”

Section: Resultsmentioning

confidence: 99%

“…Consensus clustering was performed using the ConsensuClusterPlus R package (16)(17)(18). The immune microenvironment of tumor tissue was evaluated using the estimate R package, and we calculated the evaluation scores of immune and stromal cells.…”

Section: Consensus Clustering and Its Immune Signaturementioning

confidence: 99%

N7-methylguanosine-related lncRNAs: Distinction between hot and cold tumors and construction of predictive models in colon adenocarcinoma

Cheng

Wang

et al. 2022

Front. Oncol.

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Colon adenocarcinoma (COAD) is a prevalent malignant tumor that severely threatens human health across the globe. Immunotherapy is an essential need for patients with COAD. N7-methylguanosine (m7G) has been associated with human diseases, and non-coding RNAs (lncRNAs) regulate various tumorrelated biological processes. Nonetheless, the m7G-related lncRNAs involved in COAD regulation are limited. This study aims to construct the clustering features and prognostic model of m7G-related lncRNAs in COAD. First, The Cancer Genome Atlas (TCGA) database was used to identify m7G-related differentially expressed lncRNAs (DELs), based on which COAD cases could be classified into two subtypes. Subsequently, univariate Cox analysis was used to identify 9 prognostic m7G-related lncRNAs. Further, Five candidates were screened by LASSO-Cox regression to develop new models. The patients were divided into high-risk and low-risk groups based on the median risk score. Consequently, the Kaplan-Meier survival curve demonstrated a statistically significant overall survival (OS) between the high-and low-risk groups (P<0.001). Multivariate Cox regression analysis revealed that risk score is an independent prognostic factor in COAD patients (P<0.001). This confirms the clinical applicability of the model. Additionally, we performed Gene Set Enrichment Analysis (GSEA), which uncovered the biological and functional differences between risk subgroups, i.e., enrichment of immune-related diseases in the high-risk group and enrichment of metabolic-related pathways in the low-risk group. In a drug sensitivity analysis, high-risk group were more sensitive to some chemotherapeutics and targeted drugs than lowrisk group. Eventually, the stability of the model was confirmed by qRT-PCR. Our study unraveled the features of different immune states of COAD and established a prognostic model, including five m7G-related lncRNAs for COAD Frontiers in Oncology frontiersin.org 01

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“…The molecular classification of breast cancer played a vital role in the development of precise treatment and clinical practice ( Zhao et al, 2020 ). 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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SUMOylation Pattern Predicts Prognosis and Indicates Tumor Microenvironment Infiltration Characterization in Bladder Cancer

Cited by 15 publications

References 56 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

N7-methylguanosine-related lncRNAs: Distinction between hot and cold tumors and construction of predictive models in colon adenocarcinoma

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

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