Integrative analysis of immune molecular subtypes and microenvironment characteristics of bladder cancer

Cao, Jinlong; Li, Jianpeng; Yang, Xin; Li, Pan; Yao, Zhiqiang; Han, Dali; Ying, Lijun; Wang, Lijie; Tian, Junqiang

doi:10.1002/cam4.4071

Cited by 5 publications

(6 citation statements)

References 52 publications

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“…Previous studies have found that the cluster with the lowest immune and stromal scores has a good prognosis, which may be explained by the high immune infiltration of naive CD4 + T cells ( 25 ). Another study has reported a cluster with the lowest immune cell infiltration, and the best prognosis of this cluster tends to be younger with low TNM Classification of Malignant Tumors (TNM) and clinicopathological stage ( 26 ). GSEA found that there were immunity-related signaling pathways, cancer-related pathways, and metastatic pathways in the C3 immune subtype that may be associated with a poor prognosis, whereas metabolism-related pathways were enriched in the C4 subtype ( Supplementary materials 2 ).…”

Section: Discussionmentioning

confidence: 99%

Immune landscape of distinct subtypes in urothelial carcinoma based on immune gene profile

Peng

2022

Front. Immunol.

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Immune checkpoint blockade (ICB) has become a promising therapy for multiple cancers. However, only a small proportion of patients display a limited antitumor response. The present study aimed to classify distinct immune subtypes and investigate the tumor microenvironment (TME) of urothelial carcinoma, which may help to understand treatment failure and improve the immunotherapy response. RNA-seq data and clinical parameters were obtained from TCGA-BLCA, E-MTAB-4321, and IMVigor210 datasets. A consensus cluster method was used to distinguish different immune subtypes of patients. Infiltrating immune cells, TME signatures, immune checkpoints, and immunogenic cell death modulators were evaluated in distinct immune subtypes. Dimension reduction analysis was performed to visualize the immune status of urothelial carcinoma based on graph learning. Weighted gene co-expression network analysis (WGCNA) was performed to obtain hub genes to predict responses after immunotherapy. Patients with urothelial carcinoma were classified into four distinct immune subtypes (C1, C2, C3 and C4) with various types of molecular expression, immune cell infiltration, and clinical characteristics. Patients with the C3 immune subtype displayed abundant immune cell infiltrations in the tumor microenvironment and were typically identified as “hot” tumor phenotypes, whereas those with the C4 immune subtype with few immune cell infiltrations were identified as “cold” tumor phenotypes. The immune-related and metastasis-related signaling pathways were enriched in the C3 subtype compared to the C4 subtype. In addition, tumor mutation burden, inhibitory immune checkpoints, and immunogenic cell death modulators were highly expressed in the C3 subtype. Furthermore, patients with the C4 subtype had a better probability of overall survival than patients with the C3 subtype in TCGA-BLCA and E-MTAB-4321 cohorts. Patients with the C1 subtype had the best prognosis when undergoing anti-PD-L1 antibody treatment. Finally, the immune landscape of urothelial carcinoma showed the immune status in each patient, and TGFB3 was identified as a potential biomarker for the prediction of immunotherapy resistance after anti-PD-L1 monoclonal antibody treatment. The present study provided a bioinformatics basis for understanding the immune landscape of the tumor microenvironment of urothelial carcinoma.

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Section: Discussionmentioning

confidence: 99%

Immune landscape of distinct subtypes in urothelial carcinoma based on immune gene profile

Peng

2022

Front. Immunol.

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“…Cao et al. generated a 79‐gene decision tree model to separate immune molecular subtypes and microenvironment characteristics of bladder cancer 19 . However, most of the gene signatures only focused on the tumor microenvironment, not the tumor immune infiltration features.…”

Section: Discussionmentioning

confidence: 99%

Identification of tumor immunophenotypes associated with immunotherapy response in bladder cancer

Liang,

Liao,

Yang

et al. 2023

Int J of Urology

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ObjectivesThis study aims to reveal immunophenotypes associated with immunotherapy response in bladder cancer, identify the signature genes of immune subtypes, and provide new molecular targets for improving immunotherapy response.MethodsBladder cancer immunophenotypes were characterized in the bulk RNA sequencing dataset GSE32894 and Imvigor210, and gene expression signatures were established to identify the immunophenotypes. Expression of gene signatures were validated in single‐cell RNA sequencing dataset GSE145140 and human proteins expression data source. Investigation of Immunotherapy Response was performed in IMvigor210 dataset. Prognosis of tumor immunophenotypes was further analyzed.ResultsInflamed and immune‐excluded immunophenotypes were characterized based on the tumor immune cell scores. Risk score models that were established rely on RNA sequencing profiles and overall survival of bladder cancer cohorts. The inflamed tumors had lower risk scores, and the low‐risk tumors were more likely to respond to atezolizumab, receiving complete response/partial response (CR/PR). Patients who responded to atezolizumab had higher SRRM4 and lower NPHS1 and TMEM72 expression than the non‐responders. SRRM4 expression was a protective factor for bladder cancer prognosis, while the NPHS1 and TMEM72 showed the opposite pattern.ConclusionThis study provided a novel classification method for tumor immunophenotypes. Bladder cancer immunophenotypes can predict the response to immune checkpoint blockade. The immunophenotypes can be identified by the expression of signature genes.

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“…BCa is the ninth most common cancer worldwide and urothelial carcinoma accounts for 90% of all BCa cases [18][19][20]. Recently, it has been reported that the inducing accumulation of ubiquitinated proteins was considered as a vital treatment option for BCa [12].…”

Section: Discussionmentioning

confidence: 99%

Ubiquitination-Related Molecular Subtypes and a Novel Prognostic Index for Bladder Cancer Patients

Cai¹,

Chen²,

Huang³

et al. 2021

Pathol. Oncol. Res.

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Objective: To develop and validate ubiquitination-related molecular subtypes and a novel prognostic index using ubiquitination-related genes (URGs) for patients with bladder cancer (BCa).Materials and Methods: We downloaded the clinical data and transcriptome data of BCa from TCGA and GEO database. Consensus clustering analysis was conducted to identify ubiquitination-related molecular subtypes for BCa. Besides, we performed univariate and multivariate Cox regression analysis to develop a novel prognostic URGs-related index for BCa. We conducted internal and external verification in TCGA cohort and GEO cohort, respectively. Furthermore, the associations of ubiquitination-related molecular subtypes and prognostic index with tumor immune environment were also investigated.Results: A total of four ubiquitination-related molecular subtypes of BCa were finally identified. These four molecular subtypes had significantly different clinical characteristics, prognosis, PD-L1 expression level and tumor microenvironment. Besides, we developed a novel prognostic index using six URGs (including HLA-A, TMEM129, UBE2D1, UBE2N, UBE2T and USP5). The difference in OS between high and low-risk group was statistically significant in training cohort, testing cohort, and validating cohort. The area under ROC curve (AUC) for OS prediction was 0.736, 0.723, and 0.683 in training cohort, testing cohort, and validating cohort, respectively. Multivariate survival analysis showed that this index was an independent predictor for OS. This prognostic index was especially suitable for subtype 1 and 3, older, male, high grade, AJCC stage III-IV, stage N0, stage T3-4 BCa patients.Conclusions: This study identified a total of four ubiquitination-related molecular subtypes with significantly different tumor microenvironment, prognosis, clinical characteristics and PD-L1 expression level. Besides, a novel ubiquitination-related prognostic index for BCa patients was developed and successfully verified, which performed well in predicting prognosis of BCa.

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Integrative analysis of immune molecular subtypes and microenvironment characteristics of bladder cancer

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 5 publications

References 52 publications

Immune landscape of distinct subtypes in urothelial carcinoma based on immune gene profile

Immune landscape of distinct subtypes in urothelial carcinoma based on immune gene profile

Identification of tumor immunophenotypes associated with immunotherapy response in bladder cancer

Ubiquitination-Related Molecular Subtypes and a Novel Prognostic Index for Bladder Cancer Patients

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