High expression of PYCARD is an independent predictor of unfavorable prognosis and chemotherapy resistance in glioma

Liang, Aijun; Zhong, Sen; Xi, Bin; Zhou, Chaoyang; Jiang, Xingxing; Zhu, Ronglan; Yang, Yu; Zhong, Liangchen; Wan, Dengfeng

doi:10.21037/atm-21-2346

Cited by 10 publications

(9 citation statements)

References 40 publications

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“…PYCARD, the adaptor protein of inflammasome, plays an important role in tumor carcinogenesis and progression, as confirmed by increasing evidence [ 14 , 54 ]. In our study, we found that PYCARD expression varied among human cancers and correlated to prognosis.…”

Section: Discussionmentioning

confidence: 92%

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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

Tian

et al. 2022

Cancers

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PYCARD is a protein engaged in inflammation, pyroptosis, and apoptosis. However, the function of PYCARD in human cancers remains unclear. The objective of our study was to explore PYCARD expression and prognostic value in human cancers. Public databases were used to assess PYCARD expression and prognostic value. The TISIDB database was used to explore the associations between PYCARD expression and different immune subtypes. The correlations between PYCARD expression and ICP genes, MMR genes, MSI, and TMB were also investigated. The immunotherapy response was assessed using the TIDE database. Single-cell RNA databases evaluated the PYCARD expression of immune cells. External datasets and immunohistochemical staining were conducted to validate PYCARD expression and prognostic value. The results showed that PYCARD expression varied in several cancers and was associated with prognosis, immune-related genes, published biomarkers, and immunotherapy response. Of note, PYCARD expression was upregulated in renal cancers with high diagnostic ability. Upregulation of PYCARD was correlated with worse prognosis in KIRC and external validation cohorts. In conclusion, PYCARD demonstrated strong correlations with prognosis, immune response, and disease progression in pan-cancer analysis. In ccRCC, PYCARD might serve as a biomarker for diagnosis and therapeutic target-boosting immunotherapy response.

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Section: Discussionmentioning

confidence: 92%

“…It is interesting to note that PYCARD silencing did not influence apoptosis-related expression levels in cancer cell lines. In glioma, similarly, ectopic PYCARD expression increased the viability and migration abilities of tumor cells [ 54 ]. These studies appeared to be independent of the pro-apoptotic effects of PYCARD.…”

Section: Discussionmentioning

confidence: 99%

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

Tian

et al. 2022

Cancers

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“…CASP9 is a protein-coding gene, and many reports have shown that CASP9 gene polymorphisms are associated with increased tumor risk, but this conclusion is controversial [31,32]. In gliomas, high expression of PYCARD is related to poor patient prognosis and is used as an independent predictor of chemoresistance [33]. However, the model shows high risk is positively associated with low overall survival as well as higher stage, and targeting these genes is a new option for therapy of ccRCC sick persons.…”

Section: Discussionmentioning

confidence: 99%

A Predictive Model Based on Pyroptosis-Related Gene Features Can Effectively Predict Clear Cell Renal Cell Carcinoma Prognosis and May Be an Underlying Target for Immunotherapy

et al. 2022

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Background and Objective. Recent studies show that pyroptosis-related gene affects tumor cell proliferation, invasion, and migration. But the diagnostic and prognostic value of pyroptosis-related gene in clear cell renal cell carcinoma (ccRCC) is unknown. In the present research, a prognosis model according to pyroptosis-related gene was established to forecast prognosis among patients with ccRCC. Methods. The clinical information and RNA-seq data of ccRCC patients were collected from the TCGA dataset to first explore differential pyroptosis-related genes (PRGs). Univariate Cox regression and consensus clustering were applied to identify ccRCC subtypes. The prognostic PRGs were subjected to LASSO regression analysis to establish a prognostic model and to investigate its value and function. Finally, the relationship of the model immunity checkpoints and immunity infiltration was assessed. Results. The receiver operating characteristic (ROC) showed that the 1-year, 3-year, and 5-year prediction rates of the prognostic model were 0.715, 0.693, and 0.732, respectively. The high-risk group had lower overall survival and higher stage than the low-risk group. Functional enrichment analysis showed that PRGs were significantly enriched mainly in the PPAR pathway, inflammatory pathway, and immune activity. ccRCC patient prognosis correlates with immune components in the microenvironment, and immune checkpoint molecules are significantly expressed in the high-risk group. Immunotherapy may be effective in the high-risk group. Conclusion. Pyroptosis-related gene has an important impact on the progression of ccRCC and can be used as an independent predictor of patient prognosis. In addition, immune checkpoint molecules are significantly upregulated in high-risk populations, which may be a potential target for immunotherapy.

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“…PRKACA is one of the catalytic subunits of protein kinase A, and was found to mediate resistance to HER2-targeted therapy in breast cancer [49]. PYCARD is an adaptor protein that assembles the in ammasome, high expression of which was considered to be an independent predictor of unfavorable prognosis in glioma and could promote glioma cell proliferation and migration [50]. SCAF11, also known as caspase-11, is a pro-in ammatory enzyme, which may have a role in cancer-associated angiogenesis [51].…”

Section: Discussionmentioning

confidence: 99%

A novel prognostic model based on pyroptosis-related genes for multiple myeloma

Zhang

Chen

2022

Preprint

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Background: Multiple myeloma (MM) is an incurable, relapse-prone disease with apparent prognostic heterogeneity. At present, the risk stratification of myeloma is still incomplete. Pyroptosis, a type of programmed cell death, has been shown to regulate tumor growth, and may have potential prognostic value. However, the role of pyroptosis-related genes (PRGs) in MM remains undetermined. The aim of this study was to to identify potential prognostic biomarkers and construct a predictive model related to PRGs. Methods: Sequencing and clinical data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Non-negative matrix factorization (NMF) was performed to identify molecular subtypes screening. LASSO regression was used to screen for prognostic markers. Maxstat package was utilized to calculate the optimal cutoff value for the risk score's ability. Patients were then divided into high/low risk groups depending on the cutoff value, and survival curves were plotted using the Kaplan-Meier (K-M) method. The nomogram and a calibration curve of the multi-factor model was established using the rms package. Results: A total of 33 PRGs were extracted from TCGA database underlying which 4 MM molecular subtypes were defined. Patients in cluster 1 had poorer survival than those in cluster 2 (p = 0.035), and the infiltration degree of many immune cells was the opposite in these two clusters. A total of 9 PRGs were screened out as prognostic markers, and the risk score consisting of which had the best predictive ability of 3-year survival (AUC=0.658). Patients in the high-risk group have worse survival than those in the low-risk group (p ＜ 0.0001), consisting of the results verified by GSE2658 dataset. The nomogram constructed by gender, age, ISS stage and risk score had the better prognostic predictive performance with a c-index of 0.721. Conclusions: Our model could enhance the predictive ability of ISS staging and give a reference for clinical decision-making. The new prognostic pyroptosis-related markers in MM screened out by us may facilitate the development of novel risk stratification for MM. Clinical trial registration: Not applicable.

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High expression of PYCARD is an independent predictor of unfavorable prognosis and chemotherapy resistance in glioma

Cited by 10 publications

References 40 publications

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

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

A Predictive Model Based on Pyroptosis-Related Gene Features Can Effectively Predict Clear Cell Renal Cell Carcinoma Prognosis and May Be an Underlying Target for Immunotherapy

A novel prognostic model based on pyroptosis-related genes for multiple myeloma

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