Identification of Pyroptosis-Related Gene Signatures and Construction of the Risk Model to Predict BCR in Prostate Cancer

Wang, Miaomiao; Xia, Haoran; Yan, Qiuxia; Li, Wen; Liu, Ming; Wang, Xuan

doi:10.3389/fmolb.2022.850758

Cited by 11 publications

(10 citation statements)

References 47 publications

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“…Different from the direct use of Lasso to build a prognostic model of eight pyroptosis-related genes in the study of Wang et al. ( 47 ), we used random forest dimensionality reduction and screening methods and further used Lasso analysis to build a predictive model. This analytical approach may help improve the predictive accuracy of the risk model signature.…”

Section: Discussionmentioning

confidence: 99%

Identification of pyroptosis-related lncRNA signature and AC005253.1 as a pyroptosis-related oncogene in prostate cancer

Tang

2022

Front. Oncol.

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BackgroundPyroptosis and prostate cancer (PCa) are closely related. The role of pyroptosis-related long non-coding RNAs (lncRNAs) (PRLs) in PCa remains elusive. This study aimed to explore the relationship between PRL and PCa prognosis.MethodsGene expression and clinical signatures were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. A PRL risk prediction model was established by survival random forest analysis and least absolute shrinkage and selection operator regression. Functional enrichment, immune status, immune checkpoints, genetic mutations, and drug susceptibility analyses related to risk scores were performed by the single-sample gene set enrichment analysis, gene set variation analysis, and copy number variation analysis. PRL expression was verified in PCa cells. Cell Counting Kit-8, 5-ethynyl-2′-deoxyuridine, wound healing, transwell, and Western blotting assay were used to detect the proliferation, migration, invasion, and pyroptosis of PCa cells, respectively.ResultsPrognostic features based on six PRL (AC129507.1, AC005253.1, AC127502.2, AC068580.3, LIMD1-AS1, and LINC01852) were constructed, and patients in the high-score group had a worse prognosis than those in the low-score group. This feature was determined to be independent by Cox regression analysis, and the area under the curve of the 1-, 3-, and 5-year receiver operating characteristic curves in the testing cohort was 1, 0.93, and 0.92, respectively. Moreover, the external cohort validation confirmed the robustness of the PRL risk prediction model. There was a clear distinction between the immune status of the two groups. The expression of multiple immune checkpoints was also reduced in the high-score group. Gene mutation proportion in the high-score group increased, and the sensitivity to drugs increased significantly. Six PRLs were upregulated in PCa cells. Silencing of AC005253.1 inhibited cell proliferation, migration, and invasion in DU145 and PC-3 cells. Moreover, silencing of AC005253.1 promoted pyroptosis and inflammasome AIM2 expression.ConclusionsOverall, we constructed a prognostic model of PCa with six PRLs and identified their expression in PCa cells. The experimental verification showed that AC005253.1 could affect the proliferation, migration, and invasion abilities of PCa cells. Meanwhile, AC005253.1 may play an important role in PCa by affecting pyroptosis through the AIM2 inflammasome. This result requires further research for verification.

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Section: Discussionmentioning

confidence: 99%

Identification of pyroptosis-related lncRNA signature and AC005253.1 as a pyroptosis-related oncogene in prostate cancer

Tang

2022

Front. Oncol.

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“…The tumor microenvironment (TME) has been shown to play a key role in tumorigenesis, immune progression, escape and metastasis. Wang et al further validated the relationship between the pyroptosis subtype and TME of PCa (48). Pyroptosis, as an inflammatory programmed cell death, is involved in the host protective immunity (49), which may lead to alterations of the immune microenvironment.…”

Section: Prostate Cancermentioning

confidence: 98%

Relationship between pyroptosis-mediated inflammation and the pathogenesis of prostate disease

Zhao

Guo²,

Gao³

et al. 2023

Front. Med.

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The largest solid organ of the male genitalia, the prostate gland, is comprised of a variety of cells such as prostate epithelial cells, smooth muscle cells, fibroblasts, and endothelial cells. Prostate diseases, especially prostate cancer and prostatitis, are often accompanied by acute/chronic inflammatory responses or even cell death. Pyroptosis, a cell death distinct from necrosis and apoptosis, which mediate inflammation may be closely associated with the development of prostate disease. Pyroptosis is characterized by inflammasome activation via pattern recognition receptors (PRR) upon recognition of external stimuli, which is manifested downstream by translocation of gasdermin (GSDM) protein to the membrane to form pores and release of inflammatory factors interleukin (IL)-1β and IL-18, a process that is Caspase-dependent. Over the past number of years, many studies have investigated the role of inflammation in prostate disease and have suggested that pyroptosis may be an important driver. Understanding the precise mechanism is of major consequence for the development of targeted therapeutic strategies. This review summarizes the molecular mechanisms, regulation, and cellular effects of pyroptosis briefly and then discuss the current pyroptosis studies in prostate disease research and the inspiration for us.

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“…[ 107 ] Similarly, Wang et al constructed and validated a risk model based on 8 PRGs, which demonstrated that pyroptosis was associated with tumor immune cell infiltration in PCa. [ 104 ] Zhang et al established a signature consisting of 7 genes by Lasso regression analysis. It can effectively stratify the risk of PCa patients into subgroups that are more suitable for immunotherapy and potentially serve as indicators of response to immunotherapy for PCa.…”

Section: Role Of Pyroptosis In Pcamentioning

confidence: 99%

A review focusing on the role of pyroptosis in prostate cancer

Liu,

Kuang,

Chen

2023

Medicine

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As one of the types of programmed cell death, pyroptosis has become a focus of research in recent years. Numerous studies have shown that pyroptosis plays a regulatory role in tumor cell invasiveness, differentiation, proliferation, and metastasis. It has been demonstrated that pyroptosis is involved in the regulation of signaling pathways implicated in the pathogenesis of prostate cancer (PCa). Furthermore, the loss of expression of pyroptosis-related genes in PCa has been reported, and pyroptosis-related genes have demonstrated a considerable ability in predicting the prognosis of PCa. Therefore, the potential role of pyroptosis in regulating the development of PCa warrants further investigation and attention. In this review, we summarize the basics of the role of pyroptosis and also discuss research into the mechanisms of action associated with pyroptosis in PCa. It is hoped that by exploring the potential of the pyroptosis pathway in intervening in PCa, it will provide a viable direction for the diversification of PCa treatment.

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Identification of Pyroptosis-Related Gene Signatures and Construction of the Risk Model to Predict BCR in Prostate Cancer

Cited by 11 publications

References 47 publications

Identification of pyroptosis-related lncRNA signature and AC005253.1 as a pyroptosis-related oncogene in prostate cancer

Identification of pyroptosis-related lncRNA signature and AC005253.1 as a pyroptosis-related oncogene in prostate cancer

Relationship between pyroptosis-mediated inflammation and the pathogenesis of prostate disease

A review focusing on the role of pyroptosis in prostate cancer

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