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Frontiers in Pharmacology
Article . 2022 . Peer-reviewed
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PubMed Central
Other literature type . 2022
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Frontiers in Pharmacology
Article . 2022
Data sources: DOAJ
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The Relationship of Pyroptosis-Related Genes, Patient Outcomes, and Tumor-Infiltrating Cells in Bladder Urothelial Carcinoma (BLCA)

Authors: Ruiyan Xie; Ming Xie; Litong Zhu; Joanne W. Y. Chiu; Wayne Lam; Desmond Y. H. Yap;

The Relationship of Pyroptosis-Related Genes, Patient Outcomes, and Tumor-Infiltrating Cells in Bladder Urothelial Carcinoma (BLCA)

Abstract

Introduction: The role of pyroptosis and its effects on tumor-infiltrating cells (TICs) in the pathogenesis and treatment outcomes of patients with bladder urothelial carcinoma (BLCA) remains unclear.Methods: We conducted a bioinformatics analysis on the pyroptosis-related genes (PRGs) and TICs using data from public domains, and evaluated their impact on the pathogenesis and clinical outcomes of BLCA patients. A risk score based on PRGs and a prognostic risk model that incorporated patient demographics, tumor characteristics, and differentially expressed genes (DEGs) were developed.Results: Twenty-three DEGs of 52 PRGs were identified in BLCA and normal samples from the TCGA database. Missense mutations and single nucleotide polymorphisms in PRGs are the most common genetic abnormalities. Patients with high PRG risk scores showed an inferior survival compared to those with low risk scores. The prognostic risk model based on patient demographics, tumor characteristics, and DEGs showed good predictive values for patient survival at 1, 3, and 5 years in BLCA patients. Caspase-8 (CASP8) was the only intersection gene of the prognostic genes, DEGs, and different genes expressed in tissue. Patients with a high CASP8 expression had improved survival, and an increased CASP8 expression level was observed in activated CD4 memory T cells, follicular T helper cells, resting NK cells, M0 macrophages, and activated dendritic cells. CASP8 expression also showed a positive correlation with the IL7R expression—a key cell marker of CD4 memory T cells. CASP8 expression also showed correlations with immune checkpoints (PDCD1, CD274, and CTLA4) and response to immune checkpoint inhibitors.Conclusion: Our data suggest that PRGs, especially CASP8, showed strong associations with patient outcomes and TICs in BLCA. If validated, these results could potentially aid in the prognostication and guide treatment in BLCA patients.

Related Organizations
Keywords

bladder urothelial carcinoma, Pharmacology, immune cells, CASP8, pyrotosis, immunotherapy, Therapeutics. Pharmacology, RM1-950

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
3
Top 10%
Average
Average
Green
gold