Identification of a Novel Tumor Microenvironment Prognostic Signature for Bladder Urothelial Carcinoma

Xu, Chaojie; Pei, Dongchen; Liu, Yi; Yu, Yang; Guo, Jin-Hua; Liu, Nan; Kang, Zhengjun

doi:10.3389/fonc.2022.818860

Cited by 14 publications

(11 citation statements)

References 37 publications

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“…RORB has two different isoforms, RORb1 and RORb2, and RORb2 is mainly expressed in retina and pineal gland (78). Recently, studies have found that these two genes play an important regulatory role in the development and progression of various cancers (79)(80)(81). CABP4 has been reported to be associated with the TME of urothelial carcinoma of the bladder currently (79).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, studies have found that these two genes play an important regulatory role in the development and progression of various cancers (79)(80)(81). CABP4 has been reported to be associated with the TME of urothelial carcinoma of the bladder currently (79). RORB can down-regulate the activity of Wnt signaling pathway, thus inhibiting the stemness of gastric cancer cells (82).…”

Section: Discussionmentioning

confidence: 99%

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Dysregulation of B7 family and its association with tumor microenvironment in uveal melanoma

Chen

Zheng²,

Zhang³

et al. 2022

Front. Immunol.

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BackgroundUveal melanoma (UVM) is the most common primary intraocular malignancy in adults with a poor prognosis. B7 family is an important modulator of the immune response. However, its dysregulation and underlying molecular mechanism in UVM still remains unclear.MethodsData were derived from TCGA and GEO databases. The prognosis was analyzed by Kaplan-Meier curve. The ESTIMATE algorithm, CIBERSORT algorithm, and TIMER database were used to demonstrate the correlation between B7 family and tumor immune microenvironment in UVM. Single-cell RNA sequencing was used to detect the expression levels of the B7 family in different cell types of UVM. UVM was classified into different types by consistent clustering. Enrichment analysis revealed downstream signaling pathways of the B7 family. The interaction between different cell types was visualized by cell chat.ResultsThe expression level of B7 family in UVM was significantly dysregulated and negatively correlated with methylation level. The expression of B7 family was associated with prognosis and immune infiltration, and B7 family plays an important role in the tumor microenvironment (TME). B7 family members were highly expressed in monocytes/macrophages of UVM compared with other cell types. Immune response and visual perception were the main functions affected by B7 family. The result of cell chat showed that the interaction between photoreceptor cells and immune-related cells was mainly generated by HLA-C-CD8A. CABP4, KCNJ10 and RORB had the strongest correlation with HLA-C-CD8A, and their high expression was significantly correlated with poor prognosis. CABP4 and RORB were specifically expressed in photoreceptor cells.ConclusionsDysregulation of the B7 family in UVM is associated with poor prognosis and affects the tumor immune microenvironment. CABP4 and RORB can serve as potential therapeutic targets for UVM, which can be regulated by the B7 family to affect the visual perception and immune response function of the eye, thus influencing the prognosis of UVM.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Dysregulation of B7 family and its association with tumor microenvironment in uveal melanoma

Chen

Zheng²,

Zhang³

et al. 2022

Front. Immunol.

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“…First, Kaplan-Meier curves were made to look for differences in prognosis. Moreover, the predictive value was verified by analyzing the time dependence of the receiver operating characteristic (ROC) curves ( Xu et al, 2022a ).…”

Section: Methodsmentioning

confidence: 99%

“…Bladder urothelial carcinoma (BLCA) is a common malignant tumor in the bladder system, which was listed as one of the nine most common cancers by the World Health Organization (WHO). Based on histopathology, BLCA can be classified into two categories, muscle-invasive bladder cancer (MIBC) takes most of the BLCA, which is prone to recurrence, another type that accounts for 30% is non-muscle-invasive bladder cancer (NMIBC) with rapid metastasize and low survival rate ( Xu et al, 2022a ; Kubrak et al, 2022 ). Therefore, we urgently need a prognostic risk model to provide guidance for the treatment of BLCA.…”

Section: Introductionmentioning

confidence: 99%

Clinical value of M1 macrophage-related genes identification in bladder urothelial carcinoma and in vitro validation

Huang

et al. 2022

Front. Genet.

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Background: Tumor microenvironment (TME) takes a non-negligible role in the progression and metastasis of bladder urothelial carcinoma (BLCA) and tumor development could be inhibited by macrophage M1 in TME. The role of macrophage M1-related genes in BLCA adjuvant therapy has not been studied well.Methods: CIBERSOR algorithm was applied for identification tumor-infiltrating immune cells (TICs) subtypes of subjects from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data sets. We identified potential modules of M1 macrophages by weighted gene co-expression network analysis (WGCNA). Nomogram was determined by one-way Cox regression and lasso regression analysis for M1 macrophage genes. The data from GEO are taken to verify the models externally. Kaplan-Meier and receiver operating characteristic (ROC) curves validated prognostic value of M1 macrophage genes. Finally, we divided patients into the low-risk group (LRG) and the high-risk group (HRG) based on the median risk score (RS), and the predictive value of RS in patients with BLCA immunotherapy and chemotherapy was investigated. Bladder cancer (T24, 5637, and BIU-87) and bladder uroepithelial cell line (SV-HUC-1) were used for in vitro validation. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed to validate the associated genes mRNA level.Results: 111 macrophage M1-related genes were identified using WGCNA. RS model containing three prognostically significant M1 macrophage-associated genes (FBXO6, OAS1, and TMEM229B) was formed by multiple Cox analysis, and a polygenic risk model and a comprehensive prognostic line plot was developed. The calibration curve clarified RS was a good predictor of prognosis. Patients in the LRG were more suitable for programmed cell death protein 1 (PD1) and cytotoxic T lymphocyte associate protein-4 (CTLA4) combination immunotherapy. Finally, chemotherapeutic drug models showed patients in the LRG were more sensitive to gemcitabine and mitomycin. RT-qPCR result elucidated the upregulation of FBXO6, TMEM229B, and downregulation of OAS1 in BLCA cell lines.Conclusion: A predictive model based on M1 macrophage-related genes can help guide us in the treatment of BLCA.

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“…This is due to the lack of effective biomarkers or tools to accurately judge the clinical response and prognosis of patients with BLCA. Therefore, the development and application of various biological detection and informatics techniques to show the difference in prognosis of BLCA patients according to their biological heterogeneity is essential for the treatment of BLCA and improvement of its prognosis [ 7 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of Immune-Related Subtypes and Construction of a Novel Prognostic Model for Bladder Urothelial Cancer

et al. 2022

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The purpose of this study was to explore the relationship between bladder urothelial cancer (BLCA) and immunity, to screen prognosis-related immune genes (PIGs), and to construct an immune-related prognosis model (IRPM). We processed the relevant data of The Cancer Genome Atlas (TCGA-BLCA) and GSE13507 using R software and Perl. We divided BLCA into high-immunity and low-immunity subtypes. There were significant differences in the two subtypes. In addition, we identified 13 PIGs of BLCA by jointly analyzing the gene expression data and survival information of GSE13507 and TCGA-BLCA, and constructed IRPM through nine of them. The low-risk group had better survival outcome than the high-risk group. We also constructed a nomogram based on clinicopathological information and risk scores of the patients. Moreover, the prognosis of BLCA patients was significantly impacted by the expression of almost every gene used to calculate the risk score. The result of real-time fluorescence quantitative polymerase chain reaction revealed that all the genes used to calculate the risk score were differentially expressed between BLCA and adjacent normal tissues, except PDGFRA. Our research provided potential targets for the treatment of BLCA and a reference for judging the prognosis of BLCA.

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Identification of a Novel Tumor Microenvironment Prognostic Signature for Bladder Urothelial Carcinoma

Cited by 14 publications

References 37 publications

Dysregulation of B7 family and its association with tumor microenvironment in uveal melanoma

Dysregulation of B7 family and its association with tumor microenvironment in uveal melanoma

Clinical value of M1 macrophage-related genes identification in bladder urothelial carcinoma and in vitro validation

Identification of Immune-Related Subtypes and Construction of a Novel Prognostic Model for Bladder Urothelial Cancer

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