DOI: 10.1177/03000605261488784 ISSN: 0300-0605
Integrative network toxicology and transcriptomic analyses identify
DCP1B
and
HAS2
as key prognostic biomarkers in formaldehyde-associated Wilms tumor
Gui Jun Li, Sheng Zhang, Li Na Chang, Zhong Xian Li, Yang Yang Duan, Qi Liu
Background and objectives
Wilms tumor, a common childhood malignancy, has been hypothesized to be associated with environmental factors such as formaldehyde exposure. As a potential endocrine disruptor with reported pro-proliferative effects, the molecular mechanism underlying the role of formaldehyde in Wilms tumor remains unclear. This study systematically investigated the mechanisms linking formaldehyde exposure to Wilms tumor using network toxicology and transcriptomic analysis.
Methods
Transcriptomic data were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases, whereas formaldehyde-related targets were predicted using the Search Tool for Interactions of Chemicals and Comparative Toxicogenomics databases. Candidate genes were screened through differential expression (|log2FC| > 2.5,
p
< 0.05) and weighted gene coexpression network analyses. Prognostic key genes were identified using univariate and Lasso-Cox regression, with nomogram construction and survival analysis. Single-cell RNA sequencing data (GSE223373) were further analyzed to characterize cellular heterogeneity and the cell-type-specific expression patterns of the identified key genes.
Results
Seventy-nine candidate genes associated with Wilms tumor were identified using multidimensional intersection analysis. These genes were significantly involved in pathways such as microRNAs in cancer and the cell cycle. Univariate Cox and Lasso-Cox regression analyses identified
DCP1B
and
HAS2
as key genes closely associated with the prognosis of patients with Wilms tumor. Kaplan–Meier survival analysis demonstrated that higher expressions of
DCP1B
and
HAS2
were significantly associated with better overall survival in these patients. The nomogram model constructed based on the two key genes demonstrated excellent calibration (area under the curve > 0.8) and clinical applicability. Network analysis identified
NEAT1
, the hsa-let-7 microRNA, and transcription factors such as
PDX1
and
E2F1
were as core regulatory nodes. Single-cell analysis demonstrated pronounced stromal expansion within Wilms tumor specimens and further revealed that
DCP1B
was preferentially enriched in tumor epithelial cells, whereas
HAS2
exhibited a stromal-skewed distribution, predominantly within mesangial cells.
Conclusions
DCP1B
and
HAS2
were identified as key prognostic genes for Wilms tumor. These findings suggest that formaldehyde exposure is associated with Wilms tumor pathogenesis through the potential involvement of cancer-associated microRNA pathways and cell cycle signaling, which could contribute to dysregulated cell proliferation and apoptosis.