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Research Paper|Volume 14, Issue 2|pp 989—1013

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

Haochen Yu1,2, Yong Fu3, Zhenrong Tang1, Linshan Jiang1, Chi Qu1, Han Li1, Zhaofu Tan1, Dan Shu1, Yang Peng1, Shengchun Liu1
  • 1Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
  • 2Medical Faculty of Ludwig-Maximilians-University of Munich, University Hospital of LMU Munich, Munich, Germany
  • 3Department of Breast Surgery, Dianjiang People’s Hospital of Chongqing, Chongqing, China
Received: October 5, 2021Accepted: January 21, 2022Published: January 27, 2022
https://doi.org/10.18632/aging.203855

Copyright: © 2022 Yu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.