The Inflammasomes Adaptor Protein PYCARD Is a Potential Pyroptosis Biomarker Related to Immune Response and Prognosis in Clear Cell Renal Cell Carcinoma

Su, Jiaqi; Tian, Xi; Xu, Wen; Anwaier, Aihetaimujiang; Ye, Shiqi; Zhu, Shuxuan; Wang, Yue; Gu, Jun; Shi, Guohai; Qu, Yuanyuan; Zhang, Hai-Liang; Ye, Dingwei

doi:10.3390/cancers14204992

Cited by 5 publications

(3 citation statements)

References 64 publications

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“…Furthermore, it has been demonstrated that the expression of PYCARD is correlated with both the response to tumor immunotherapy and prognosis. Our data indicated that elevated levels of PYCARD in BC are linked to improved overall survival (OS), although the precise mechanism is not yet clear and requires further investigation in future studies ( 52 ).…”

Section: Discussionmentioning

confidence: 85%

Predicting the immune microenvironment and prognosis with a anoikis - related signature in breast cancer

Qin

Zhang

et al. 2023

Front. Oncol.

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BackgroundTumor heterogeneity is widely recognized as a crucial factor impacting the prognosis of breast cancer (BC) patients. However, there remains an insufficient understanding of the underlying impact of anoikis on the prognosis of BC patients.MethodsThe researchers utilized the TCGA-BRCA dataset to screen and analyze the differentially expressed genes of anoikis-related genes (ARGs) in BC and normal breast tissue. Prognostic gene signatures were established through univariate, LASSO, and multivariate Cox regression analyses. These signatures were evaluated using Kaplan-Meier curve and receiver operating characteristic (ROC) analyses, resulting in the development of an anoikis-related index (ACI). The training dataset was TCGA-BRCA, while METABRIC and GSE96058 were used for external validation. Additionally, nomograms were developed by combining risk scores and clinical parameters, enabling gene set enrichment analysis (GSEA) and tumor immunoassay. Furthermore, an exploration of small molecule compounds was conducted to identify potential therapeutic benefits.ResultsA six-gene anoikis-related signature was constructed, which divided BC patients into high- and low-ACI groups based on median ACI scores. The ACI accurately predicted prognosis and acted as an independent prognostic factor for BC patients. Patients in the high-ACI group exhibited poorer overall survival (OS) across all cohorts and showed more severe clinical manifestations compared to the low-ACI group. The study also explored the potential impacts of anoikis on immune cells infiltrating tumors, immune checkpoints, growth factors, and cytokine levels. Additionally, the potential implications of anoikis in BC immunotherapy were discussed, along with highlighting small molecule compounds that could offer therapeutic benefits.ConclusionsAnoikis was found to hold significant prognostic value in breast cancer, providing a novel approach for managing patients with different prognoses and implementing more precise immunotherapy strategies.

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Section: Discussionmentioning

confidence: 85%

Predicting the immune microenvironment and prognosis with a anoikis - related signature in breast cancer

Qin

Zhang

et al. 2023

Front. Oncol.

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“…These ndings illustrated that PYCARD could be a novel and potential biomarker for COPD. The in ammasome adaptor protein PYCARD (known as ASC) is a potential pyroptosis biomarker engaged in in ammation and related to immune response [40], which provides new insights into the pathogenesis of in ammatory diseases [41][42]. In addition, regarding function enrichment analysis, we demonstrated that PYCARD was mainly related to protein modi cation process, chemical stimulus, regulation of response to stimulus, and immune system process.…”

Section: Discussionmentioning

confidence: 89%

Identification and experimental validation of PYCARD as a crucial PANoptosis-related gene for immune response and inflammation in COPD

Shi,

Liang,

Wang

et al. 2024

Apoptosis

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ObjectiveChronic in ammatory and immune responses play key roles in the development and progression of chronic obstructive pulmonary disease (COPD). PANoptosis, as a unique in ammatory cell death modality, is involved in the pathogenesis of many in ammatory diseases. We aim to identify critical PANoptosis-related biomarkers and explore their potential effects on respiratory tract diseases and immune in ltration landscapes in COPD. MethodsTotal microarray data consisting of peripheral blood and lung tissue datasets associated with COPD were obtained from the GEO database. PANoptosis-associated genes in COPD were identi ed by intersecting differentially expressed genes (DEGs) with genes involved in pyroptosis, apoptosis, and necroptosis after normalizing and removing the batch effect. Furthermore, GO, KEGG, PPI network, WGCNA, LASSO-COX, and ROC curves analysis were conducted to screen and verify hub genes, and the correlation between PYCARD and in ltrated immune cells was analyzed. The effect of PYCARD on respiratory tract diseases and the potential small-molecule agents for the treatment of COPD were identi ed. PYCARD expression was veri ed in the lung tissue of CS/LPS-induced COPD mice. ResultsPYCARD was a critical PANoptosis-related gene in all COPD patients. PYCARD was positively related to NOD-like receptor signaling pathway and promoted immune cell in ltration. Moreover, PYCARD was signi cantly activated in COPD mice mainly by targeting PANoptosis. ConclusionPANoptosis-related gene PYCARD is a potential biomarker for COPD diagnosis and treatment.

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“…PYCARD, which is commonly known as apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), is the adaptor protein of inflammasomes and plays an important role in inflammation and pyroptosis. PYCARD contains a caspase activation and recruitment domain (CARD) and a pyrin domain (PYD) (35). Recent evidence revealed a crucial role of PYCARD in renal injury after UUO, and PYCARD deficiency reduces renal inflammation and fibrosis (36).…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis reveals crosstalk between pyroptosis and immune regulation in renal fibrosis

Bai,

Han,

Yang

et al. 2024

Front. Immunol.

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PurposeThe pathogenesis of renal fibrosis (RF) involves intricate interactions between profibrotic processes and immune responses. This study aimed to explore the potential involvement of the pyroptosis signaling pathway in immune microenvironment regulation within the context of RF. Through comprehensive bioinformatics analysis and experimental validation, we investigated the influence of pyroptosis on the immune landscape in RF.MethodsWe obtained RNA-seq datasets from Gene Expression Omnibus (GEO) databases and identified Pyroptosis-Associated Regulators (PARs) through literature reviews. Systematic evaluation of alterations in 27 PARs was performed in RF and normal kidney samples, followed by relevant functional analyses. Unsupervised cluster analysis revealed distinct pyroptosis modification patterns. Using single-sample gene set enrichment analysis (ssGSEA), we examined the correlation between pyroptosis and immune infiltration. Hub regulators were identified via weighted gene coexpression network analysis (WGCNA) and further validated in a single-cell RNA-seq dataset. We also established a unilateral ureteral obstruction-induced RF mouse model to verify the expression of key regulators at the mRNA and protein levels.ResultsOur comprehensive analysis revealed altered expression of 19 PARs in RF samples compared to normal samples. Five hub regulators, namely PYCARD, CASP1, AIM2, NOD2, and CASP9, exhibited potential as biomarkers for RF. Based on these regulators, a classifier capable of distinguishing normal samples from RF samples was developed. Furthermore, we identified correlations between immune features and PARs expression, with PYCARD positively associated with regulatory T cells abundance in fibrotic tissues. Unsupervised clustering of RF samples yielded two distinct subtypes (Subtype A and Subtype B), with Subtype B characterized by active immune responses against RF. Subsequent WGCNA analysis identified PYCARD, CASP1, and NOD2 as hub PARs in the pyroptosis modification patterns. Single-cell level validation confirmed PYCARD expression in myofibroblasts, implicating its significance in the stress response of myofibroblasts to injury. In vivo experimental validation further demonstrated elevated PYCARD expression in RF, accompanied by infiltration of Foxp3+ regulatory T cells.ConclusionsOur findings suggest that pyroptosis plays a pivotal role in orchestrating the immune microenvironment of RF. This study provides valuable insights into the pathogenesis of RF and highlights potential targets for future therapeutic interventions.

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The Inflammasomes Adaptor Protein PYCARD Is a Potential Pyroptosis Biomarker Related to Immune Response and Prognosis in Clear Cell Renal Cell Carcinoma

Cited by 5 publications

References 64 publications

Predicting the immune microenvironment and prognosis with a anoikis - related signature in breast cancer

Predicting the immune microenvironment and prognosis with a anoikis - related signature in breast cancer

Identification and experimental validation of PYCARD as a crucial PANoptosis-related gene for immune response and inflammation in COPD

Integrated analysis reveals crosstalk between pyroptosis and immune regulation in renal fibrosis

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