A novel pyroptosis-related signature predicts prognosis and response to treatment in breast carcinoma

Abstract

Background: Pyroptosis is a new form of programmed cell death (PCD), also known as cellular inflammatory necrosis. Its discovery has resulted in a novel approach to the progression and medication resistance of breast cancer (BC). However, there is still a significant gap in the investigation of pyroptosis-related genes in BC. Methods: The mRNA expression profiles and clinical data of BC patients were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Then, using the TCGA cohort, we created a predictive multigene signature including pyroptosis-related genes and verified it using the two GEO cohorts. A pyroptosis-related gene signature was created by combining several bioinformatics and statistical methodologies to predict patient prognosis and responses to immunotherapy and chemotherapy. Furthermore, a nomogram based on the gene signature and clinicopathological markers was created to better classify the risk and quantify the risk assessment of individual patients. Results: A pyroptosis-related gene signature consisting of 15 genes was established. The pyroptosis-related gene signature classified the patients into two groups: high-risk and low-risk. When combined with clinical variables, the risk score was discovered to be an independent predictor of overall survival (OS) in BC patients. Some immunological pathways and genes were linked to pyroptosis, according to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) evaluations. Patients in the high-risk group had a worse prognosis and were not very sensitive to immunotherapy. However, several chemotherapeutic agents were predicted to have greater potential for patients in the high-risk group. Finally, a nomogram was developed that included a classifier based on the 15 pyroptosis-related genes, tumor stage, age, and histologic grade. This nomogram demonstrated good classification capacity and might help with clinical decision-making in BC.

A novel pyroptosis-related indicator of immune infiltration features and prognosis in breast cancer

“…As the data were obtained from public databases, they need to be validated with laboratory/real clinical data. Yu et al have identified different pyroptosis genes from us in humans through the TCGA and GEO databases (55), but the good thing is that those pyroptosis genes found by both of us can predict the prognosis of breast cancer. Therefore, in the next study, we will analyze the reported data and verify the relationship between pyroptosis genes and breast cancer through in vivo and in vitro experiments.…”

A pyroptosis expression pattern score predicts prognosis and immune microenvironment of lung squamous cell carcinoma

“…Although we did not use pyroptosis-related genes to establish models directly like most studies, the PEPScore still shows a strong association with pyroptosis ( Ye et al, 2021 ; Chen et al, 2022 ; Yang et al, 2022 ; Yu et al, 2022 ). The ROC curve shows high specificity and sensitivity for PEPScore to distinguish different pyroptotic expression patterns.…”

A risk model based on pyroptosis subtypes predicts tumor immune microenvironment and guides chemotherapy and immunotherapy in bladder cancer

“…The RNA expression data of GSE13507 dataset, generated by Illumina human-6 v2.0 expression beadchip, was converted to transcripts per kilobase million (TPM) format using R package limma for downstream analyses 22 . 57 pyroptosis-related genes (PRGs) were obtained from REACTOME database ( https://reactome.org/ ), Gene Ontology (GO) database ( http://geneontology.org ), and published articles 23 (Table S1 ). The whole analysis pipeline was shown in the flow chart (Figure S1 ).…”

“…org/), Gene Ontology (GO) database (http:// geneo ntolo gy. org), and published articles 23 (Table S1). The whole analysis pipeline was shown in the flow chart (Figure S1).…”