A Novel TGF-β Risk Score Predicts the Clinical Outcomes and Tumour Microenvironment Phenotypes in Bladder Cancer

Liu, Zhi; Qi, Tiezheng; Li, Xiaowen; Yao, Yiyan; Othmane, Belaydi; Chen, Jinbo; Zu, Xiongbing; Ou, Zhenyu; Hu, Jiao

doi:10.3389/fimmu.2021.791924

Cited by 28 publications

(19 citation statements)

References 68 publications

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“…Finally, we collected many drug targets from the Drug Bank database. These therapeutic response related signatures or molecules were reported in our previous studies ( 16 , 17 ).…”

Section: Methodssupporting

confidence: 79%

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GATA3 Predicts the Tumor Microenvironment Phenotypes and Molecular Subtypes for Bladder Carcinoma

Zhang

Liu

et al. 2022

Front. Surg.

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AimsGATA3 is a key player in antitumor immunology, and continuous studies show that it might be a key biomarker for bladder cancer (BLCA). Thus, we lucubrate the immunological role of GATA3 in BLCA.Main MethodsWe initially used pan-cancer analysis to analyze the expression pattern and immunological function of GATA3 with data gathered from the TCGA (The Cancer Genome Atlas). Then, in the BLCA tumor microenvironment (TME), we comprehensively associated GATA3 with immunomodulators, cancer immune cycles, tumor-infiltrating immune cells (TIICs), immune checkpoints, and T-cell inflamed scores(TIS). The role of GATA3 in predicting BLCA molecular subtypes and responsiveness to various treatment regimens was also investigated. We confirmed our findings in an external cohort and the Xiangya-Pingkuang cohort to guarantee the correctness of our study.Key FindingsGATA3 was preferentially expressed in the TME of numerous malignancies, including BLCA. High GATA3 expression was adversely connected with immunological aspects such as immunomodulators, cancer immune cycles, TIICs, immune checkpoints, and TIS in the BLCA TME. In addition, high GATA3 was more likely to be a luminal subtype, which meant it was less susceptible to cancer immunotherapy and neoadjuvant chemotherapy but more sensitive to targeted treatments.SignificanceGATA3 may aid in the precision treatment for BLCA because it can accurately predict the clinical outcomes and the TME characteristics of BLCA.

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“…Finally, we collected many drug targets from the Drug Bank database. These therapeutic response related signatures or molecules were reported in our previous studies ( 16 , 17 ).…”

Section: Methodssupporting

confidence: 79%

“…Finally, we also associated GATA3 with the T-cell inflamed score, which represents the level of pre-existing cancer immunity ( 16 , 19 ). These immune characters were described in detail in our previous studies ( 16 , 17 ).…”

Section: Methodsmentioning

confidence: 92%

GATA3 Predicts the Tumor Microenvironment Phenotypes and Molecular Subtypes for Bladder Carcinoma

Zhang

Liu

et al. 2022

Front. Surg.

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“…At present, TGF- β signaling pathway is widely utilized to predict the prognosis of various tumors, such as bladder cancer, hepatocellular carcinoma, and breast cancer [ 24 – 26 ]. Previous work has shown that TGF- β is essential for the tumorigenesis and invasion of head and neck squamous cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Integrated Machine Learning and Single-Sample Gene Set Enrichment Analysis Identifies a TGF-Beta Signaling Pathway Derived Score in Headneck Squamous Cell Carcinoma

Yi-lin

et al. 2022

Journal of Oncology

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Background. The TGF-β signaling pathway is clinically predictive of pan-cancer. Nevertheless, its clinical prognosis and regulation of immune microenvironment (TME) characteristics as well as the prediction of immunotherapy efficacy need to be further elucidated in head and neck squamous cell carcinoma. Method. At first, we summarized TGF-β related genes from previous published articles, used ssGSEA to establish the TGF-β risk score. Considering the complexity of its clinical application, we improved it with the LASSO-COX algorithm to construct the model. In addition, we explored the predictive efficacy of TGF-β risk score in the observation of TME phenotype and immunotherapy effect. Finally, the potency of TGF-β risk score in adjusting precise treatment of HNSC was evaluated. Results. We systematically established TGF-β risk score with multi-level predictive ability. TGF-β risk score was employed to predict the tumor microenvironment status, which was negatively associated with NK cells but positively related to macrophages and fibroblasts. It reveals that patients with high TGF-β risk score predict “cold” TME status. In addition, higher risk scores indicate higher sensitivity to immunotherapy. Conclusion. We first construct and validate TGF-β characteristics that can predict immune microenvironment phenotypes and immunotherapeutic effect in multiple datasets. Noteworthy, TGF-β risk score is helpful for individualized precise treatment of patients with the head and neck squamous cell carcinoma.

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“…Xiangya cohort: According to our previous study, the Xiangya cohort (GSE188715) comprised 57 BLCA samples sequenced on the BGISEQ-500 platform (BGI-Shenzhen, China) (13)(14)(15). Determination of pyroptosis gene sets: The keyword "pyroptosis" was searched in the GSEA public database (http://www.gsea-msigdb.org/gsea/msigdb/genesets.jsp).…”

Section: Data Sets Collection External Public Cohortsmentioning

confidence: 99%

Robust pyroptosis risk score guides the treatment options and predicts the prognosis of bladder carcinoma

Deng

Liu

et al. 2022

Front. Immunol.

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BackgroundBladder carcinoma (BLCA) is a heterogeneous disease that makes it difficult to achieve proper individual treatment and predict prognosis. This study aimed to develop a risk score from a new perspective of pyroptosis and guide accurate treatment and prognosis prediction for BLCA.MethodsThe TCGA-BLCA cohort data were downloaded from The Cancer Genome Atlas database. Two external validation cohorts were collected from the Gene Expression Omnibus. Another independent validation cohort (the Xiangya cohort) was recruited from our hospital. The least absolute shrinkage and selector operation (LASSO) algorithm and Cox regression models were used to establish the pyroptosis risk score. Thereafter, we correlated the pyroptosis risk score with prognosis, tumor microenvironment (TME) immune hallmarks, and multiple treatments, including anticancer immunotherapy, chemotherapy, radiotherapy, and targeted therapy.ResultsThe pyroptosis risk score was an independent prognostic predictor of BLCA. We found that the activities of multiple steps of the anticancer immune response cycle, such as the release of cancer cell antigens, CD8 T cell recruitment, and NK cell recruitment, were significantly higher in the high-risk score group than in the low-risk score group. In addition, the infiltration levels of the corresponding tumor-infiltrating immune cells (TIICs), such as CD8 T cells and NK cells, were positively correlated with the pyroptosis risk score. Thus, BLCA with a high-risk score may be associated with inflamed phenotypes. Simultaneously, the expression of multiple immune checkpoints (such as PD-L1, CTLA-4, and PD-1) and enrichment scores of gene signatures positively correlated with immunotherapy response were positively correlated with the pyroptosis risk score. Therefore, patients with a high pyroptosis risk score may be more sensitive to immunotherapy. In addition, patients with high pyroptosis risk scores may be more sensitive to chemotherapeutic drugs, such as cisplatin, docetaxel, and paclitaxel. In addition, the pyroptosis risk score accurately predicted the molecular subtypes of BLCA, which were cross-validated in several independent systems.ConclusionsThis study developed and validated a robust pyroptosis risk score that can predict the clinical outcomes and TME immune phenotypes of BLCA. In summary, the pyroptosis risk score helps drive precision therapy in patients with BLCA.

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A Novel TGF-β Risk Score Predicts the Clinical Outcomes and Tumour Microenvironment Phenotypes in Bladder Cancer

Cited by 28 publications

References 68 publications

GATA3 Predicts the Tumor Microenvironment Phenotypes and Molecular Subtypes for Bladder Carcinoma

GATA3 Predicts the Tumor Microenvironment Phenotypes and Molecular Subtypes for Bladder Carcinoma

Integrated Machine Learning and Single-Sample Gene Set Enrichment Analysis Identifies a TGF-Beta Signaling Pathway Derived Score in Headneck Squamous Cell Carcinoma

Robust pyroptosis risk score guides the treatment options and predicts the prognosis of bladder carcinoma

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