Genome-wide Exploration of a Pyroptosis-Related Long Non-Coding RNA Signature Associated With the Prognosis and Immune Response in Patients With Bladder Cancer

Abstract

Background: Bladder cancer (BLCA) is a malignant tumor with a complex molecular mechanism and high recurrence rate in the urinary system. Studies have shown that pyroptosis regulates tumor cell proliferation and metastasis and affects the prognosis of cancer patients. However, the role of pyroptosis-related (PR) genes or long non-coding RNAs (lncRNAs) in BLCA development is not fully understood.Methods: We comprehensively analyzed the molecular biological characteristics of PR genes in BLCA, including copy number variation, mutations, expression and prognostic value based on TCGA database. We then identified PR lncRNAs with prognostic value based on the expression of PR genes and performed a consistent clustering analysis of 407 BLCA patients according to the expression of prognosis-related PR lncRNAs and identified two clusters. The least absolute shrinkage and selection operator (LASSO) regression was used to establish a PR lncRNA signature and calculate the risk score associated with the prognosis of patients with BLCA. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) were used to evaluate the possible functions of PR lncRNA signature. We also evaluated the relationship between the risk score and tumor immune microenvironment (TIME).Results: A total of 33 PR genes were obtained in our study and 194 prognosis-related PR lncRNAs were identified. We also constructed a signature consisting of eight-PR-lncRNAs and divided patients into high- and low-risk groups. The overall survival rate of patients with a high risk was significantly lower than patients with a low risk. The risk score was significantly correlated with the degree of infiltration of multiple immune cell subtypes and positively correlated with multiple immune checkpoint genes expression in BLCA. Enrichment analyses showed that these lncRNAs are involved in human immune regulatory functions and immune-related pathways.Conclusion: Our study comprehensively studied the molecular biological characteristics of PR genes BLCA, and the eight-PR-lncRNA signature we identified might play a crucial role in tumor immunity and may be able to predict the prognosis of BLCA patients, providing a theoretical basis for an in-depth study of the relationship between the prognosis and TIME.

Relevance of pyroptosis‐associated genes in nasopharyngeal carcinoma diagnosis and subtype classification

“…Pyroptosis is a type of programmed cell death that is caused by inflammation, mediated by inflammatory vesicles, and distinguished from other types of cell death such as apoptosis, autophagy and necrosis. 13,14 The classical pathway is driven by inflammatory vesicles, such as NOD-like receptor protein 3, which triggers caspase-1 to cleave gasdermin D (GSDMD) to produce pore membranes, ultimately encouraging downstream pro-inflammatory cytokine maturation and the release of pro-interleukin (IL)-1 and pro-IL-18. 15 Atypical pyroptosis is mediated by caspase-4/5/11 and promotes local cell death by cleaving GSDMD to form -NT fragments.…”

“…Pyroptosis was first proposed in 1992 by Zychlinsky et al 12 after observing cytomorphological changes such as DNA fragmentation, vacuole formation and chromatin sequestration in macrophages infected with Shigella fowleri . Pyroptosis is a type of programmed cell death that is caused by inflammation, mediated by inflammatory vesicles, and distinguished from other types of cell death such as apoptosis, autophagy and necrosis 13,14 . The classical pathway is driven by inflammatory vesicles, such as NOD‐like receptor protein 3, which triggers caspase‐1 to cleave gasdermin D (GSDMD) to produce pore membranes, ultimately encouraging downstream pro‐inflammatory cytokine maturation and the release of pro‐interleukin (IL)‐1 and pro‐IL‐18 15 .…”