Comprehensive Analysis of Pyroptosis-Related Genes and Tumor Microenvironment Infiltration Characterization in Breast Cancer

Abstract

BackgroundImmunotherapy has emerged as a significant strategy to treat numerous tumors. The positive response to immunotherapy depends on the dynamic interaction between tumor cells and infiltrating lymphocytes in the tumor microenvironment (TME). Pyroptosis, inflammation-induced cell death, is intricately associated with several tumors. However, the relationship between pyroptosis and clinical prognosis, immune cell infiltration, and immunotherapy effect is unclear in breast cancer (BRCA).MethodsWe comprehensively evaluated 33 pyroptosis-related genes and systematically assessed the relationship between pyroptosis and tumor progression, prognosis, and immune cell infiltration. The PyroptosisScore was used to quantify the pyroptosis pattern of a single tumor patient. We then assessed their values for predicting prognoses and therapeutic responses in BRCA.ResultsThree different modes of PyroptosisClusters were determined. The characteristics of TME cell infiltration in these three PyroptosisClusters were highly consistent with three immunophenotypes of tumors, including immune-excluded, immune-inflamed, and immune-desert phenotypes. Comprehensive bioinformatics analysis revealed that patients with a low PyroptosisScore had higher immune checkpoint expression, higher immune checkpoint inhibitor (ICI) scores, increased immune microenvironment infiltration, and were more sensitive to immunotherapy than those with a high PyroptosisScore.ConclusionsOur findings revealed the crucial role of pyroptosis in maintaining the diversity and complexity of TME. Pyroptosis is closely related to tumor progression, tumor prognosis, and immunotherapy response. Evaluating the PyroptosisScore of a single tumor can assist in understanding the characteristics of TME infiltration and lead to the development of more effective immunotherapy strategies.

Comprehensive Analysis of the Correlation Between Pyroptosis-Related LncRNAs and Tumor Microenvironment, Prognosis, and Immune Infiltration in Hepatocellular Carcinoma

“…LncRNA ATB upregulates ZEB1 and ZEB2 by binding to miR-200, inducing epithelial-mesenchymal transition and HCC invasion ( Yuan et al, 2014 ). The role of pyroptosis-modified lncRNAs has been demonstrated in lung, breast, and head and neck cancers ( Liu et al, 2019 ; Wu et al, 2021 ; Zhu et al, 2021 ). However, the correlation between pyroptosis-modified lncRNAs and the TME, immune infiltration, and immune checkpoint genes in HCC remains unclear.…”

Comprehensive Pan-Cancer Analyses of Pyroptosis-Related Genes to Predict Survival and Immunotherapeutic Outcome

“…Pyroptosis may affect the immune cell microenvironment, to a certain extent, by changing the proportion of immune cells, which determine the outcome of immunotherapy [ 70 , 71 ]. Interestingly, certain genes were positively correlated with the risk scores in most cancers, while other genes were negatively correlated with the risk scores ( Figure 4 B).…”

Pan-cancer analyses of pyroptosis with functional implications for prognosis and immunotherapy in cancer

“…Our study has several advantages over previous studies on certain cancers. First, previous studies focused on the development and validation of prognostic models involving certain cancer types [32][33][34][35]. Our studies aimed to assess pyroptosis levels in cancer as a whole, and our model of pyroptosis levels is thus more universal.…”