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BMC Pediatrics
Published in: BMC Pediatrics 1/2024

Open Access 01-12-2024 | Research

A novel pyroptosis-related gene signature exhibits distinct immune cells infiltration landscape in Wilms’ tumor

Authors: Yujun Guo, Wenjun Lu, Ze’nan Zhang, Hengchen Liu, Aodan Zhang, Tingting Zhang, Yang Wu, Xiangqi Li, Shulong Yang, Qingbo Cui, Zhaozhu Li

Published in: BMC Pediatrics | Issue 1/2024

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Abstract

Background

Wilms’ tumor (WT) is the most common renal tumor in childhood. Pyroptosis, a type of inflammation-characterized and immune-related programmed cell death, has been extensively studied in multiple tumors. In the current study, we aim to construct a pyroptosis-related gene signature for predicting the prognosis of Wilms’ tumor.

Methods

We acquired RNA-seq data from TARGET kidney tumor projects for constructing a gene signature, and snRNA-seq data from GEO database for validating signature-constructing genes. Pyroptosis-related genes (PRGs) were collected from three online databases. We constructed the gene signature by Lasso Cox regression and then established a nomogram. Underlying mechanisms by which gene signature is related to overall survival states of patients were explored by immune cell infiltration analysis, differential expression analysis, and functional enrichment analysis.

Results

A pyroptosis-related gene signature was constructed with 14 PRGs, which has a moderate to high predicting capacity with 1-, 3-, and 5-year area under the curve (AUC) values of 0.78, 0.80, and 0.83, respectively. A prognosis-predicting nomogram was established by gender, stage, and risk score. Tumor-infiltrating immune cells were quantified by seven algorithms, and the expression of CD8( +) T cells, B cells, Th2 cells, dendritic cells, and type 2 macrophages are positively or negatively correlated with risk score. Two single nuclear RNA-seq samples of different histology were harnessed for validation. The distribution of signature genes was identified in various cell types.

Conclusions

We have established a pyroptosis-related 14-gene signature in WT. Moreover, the inherent roles of immune cells (CD8( +) T cells, B cells, Th2 cells, dendritic cells, and type 2 macrophages), functions of differentially expressed genes (tissue/organ development and intercellular communication), and status of signaling pathways (proteoglycans in cancer, signaling pathways regulating pluripotent of stem cells, and Wnt signaling pathway) have been elucidated, which might be employed as therapeutic targets in the future.
Appendix
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Metadata
Title
A novel pyroptosis-related gene signature exhibits distinct immune cells infiltration landscape in Wilms’ tumor
Authors
Yujun Guo
Wenjun Lu
Ze’nan Zhang
Hengchen Liu
Aodan Zhang
Tingting Zhang
Yang Wu
Xiangqi Li
Shulong Yang
Qingbo Cui
Zhaozhu Li
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Pediatrics / Issue 1/2024
Electronic ISSN: 1471-2431
DOI
https://doi.org/10.1186/s12887-024-04731-0

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