Identification and verification of the pyroptosis-related prognostic signature and its associated regulatory axis in bladder cancer

Abstract

Background: Pyroptosis is an inflammatory form of cell death triggered by certain inflammasomes. Accumulating studies have shown the involvement of pyroptosis in the proliferation, invasion, and metastasis and prognosis of cancer. The prognostic value of pyroptosis-related genes (PRGs) and their association with immune infiltration in bladder cancer have not yet been elucidated.Methods: We performed a comprehensive analysis of the prognostic value and immune infiltrates of PRGs in bladder cancer using the TCGA dataset. qRT-PCR was also performed to verify our result.Results: Among 33 PRGs, 14 PRGs were upregulated or downregulated in bladder cancer tissue versus normal tissue. We also summarized copy number variations and somatic mutations of PRGs in bladder cancer. By using consensus clustering analysis of PRGs with prognostic significance, we divided the bladder cancer cohort into two subtypes significantly by different prognosis and immune infiltration. Using the LASSO Cox regression analysis, a prognostic signature including six PRGs was constructed for bladder cancer and the patients could be classified into a low- or high-risk group. Interestingly, this prognostic signature had a favorable performance for predicting the prognosis of bladder cancer patients. Moreover, further analysis demonstrated a significant difference in gender, tumor grade, clinical stage, TNM stage, immunoScore, and immune cell infiltration between the high- and low-risk groups in bladder cancer. We also identified an lncRNA SNHG14/miR-20a-5p/CASP8 regulatory axis in bladder cancer by constructing a ceRNA network.Conclusion: We identified a PRG-associated prognostic signature associated with the prognosis and immune infiltrates for bladder cancer and targeting pyroptosis may be an alternative approach for therapy. Further vivo and vitro experiments are necessary to verify these results.

Functional investigation and two-sample Mendelian randomization study of bladder cancer-related genes: focus on gender differences

“…Recently, it has also been shown that VEGFA expression affects the immune microenvironment in bladder cancer. For example, VEGFA overexpression in bladder cancer is related to high in ltration of cd163 + tams [30]. We found that in male bladder cancer, the tissue abundance of Tregs, M0 macrophages, follicular T cells, and activated dendritic cells was positively correlated with VEGFA expression, while the tissue abundance of CD8 + T cells, resting mast cells, M2 macrophages, and CD4 + T cells was negatively correlated with VEGFA expression.…”

Construction of endothelial cell signatures for predicting the diagnosis, prognosis and immunotherapy response of bladder cancer via machine learning

“…Among all cancer types, bladder cancer (BC) ranks 13th in mortality rate. A high recurrence rate is an important feature of BC, and long‐term invasive monitoring is needed to detect tumour progression over time 1,2 . In the past few decades, limited progress has been made in treating BC, and the current main treatment methods for BC are surgery, chemotherapy and immunotherapy 3,4 .…”

“…A high recurrence rate is an important feature of BC, and longterm invasive monitoring is needed to detect tumour progression over time. 1,2 In the past few decades, limited progress has been made in treating BC, and the current main treatment methods for BC are surgery, chemotherapy and immunotherapy. 3,4 To help clinicians better predict the diagnosis, prognosis and treatment response of BC, tumour molecular markers that are associated with BC should be identified.The tumour microenvironment (TME) consists of fluids, stromal cells, and immune cells and can interact with tumour cells to promote tumour growth, metastasis, and immune escape.…”

A risk model based on lncRNA-miRNA-mRNA gene signature for predicting prognosis of patients with bladder cancer

“…lncRNA TINCR can reduce the OS rate of BC patients by inhibiting miR-7 and regulating mTOR [ 12 ]. Above all, based on the above researches, we found that the RNAs could be a potential biomarkers for BC and also were associated with BC through the ceRNA mechanism [ 13 , 14 , 15 ].…”