Hypothesis-generating network toxicology analysis of potential molecular convergence between a polystyrene oligomer proxy and papillary thyroid carcinoma
- 1Department of Head and Neck Surgery, The First Hospital of Jiaxing (Affiliated Hospital of Jiaxing University)
Abstract
Background: Polystyrene microplastics (PS-MPs) are emerging environmental contaminants with endocrine-disrupting and pro-inflammatory effects, but whether PS-MPs-associated molecular targets converge with papillary thyroid carcinoma (PTC) alterations remains unclear. This hypothesis-generating study aimed to identify candidate molecular networks and cellular contexts shared between a simplified polystyrene computational proxy and PTC.
Methods: Putative targets from CTD and from TargetNet/SwissTargetPrediction using a five-styrene-unit oligomer proxy were intersected with thyroid cancer-related genes from OMIM and GeneCards. Protein functional-association and enrichment analyses were followed by differential expression analysis in GSE33630 (45 normal and 49 PTC samples). LASSO and SVM-RFE identified core genes; stability was examined by repeated nested resampling conditional on the seven-gene candidate panel. Individual-gene tumor-normal discrimination was assessed in GSE33630 and GSE60542. Protein patterns were evaluated qualitatively in the Human Protein Atlas and preliminarily in 15 matched PTC-adjacent tissue pairs. CIBERSORT-estimated immune fractions and two single-cell datasets were analyzed as exploratory context.
Results: Among 144 putative proxy-associated targets and 2,139 thyroid cancer-related genes, 75 were shared. Seven candidates overlapped with 1,306 PTC differentially expressed genes, and BCL2, BAX, and FN1 were selected by both feature-selection methods and remained stable across the tested GeneCards thresholds and CTD-only sensitivity analysis. BCL2 was downregulated, whereas BAX and FN1 were upregulated in PTC; individual-gene AUCs were 0.963, 0.941, and 0.965 in GSE33630 and 0.942, 0.907, and 0.955 in GSE60542. HPA images and clinical IHC supported the same protein-level directions. After multiple-testing correction, only the CIBERSORT-estimated neutrophil fraction differed between groups (higher in PTC; q=0.0021). Single-cell analysis localized the three genes across epithelial, stromal, and immune compartments.
Conclusion: BCL2, BAX, and FN1 are candidate molecular nodes at the convergence of polystyrene-proxy annotations and PTC-associated alterations. The findings do not demonstrate patient PS-MPs exposure, intact-particle effects, or causality, and require validation in material-characterized exposure experiments and exposure-aware clinical studies.
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BibTeX
@article{xie2026hypothesisgenerating,
title = {{Hypothesis-generating network toxicology analysis of potential molecular convergence between a polystyrene oligomer proxy and papillary thyroid carcinoma}},
author = {Weidong Xie and Jian Tang and Xiaoyu Qian},
journal = {Frontiers in Endocrinology},
year = {2026},
month = oct,
doi = {10.3389/fendo.2026.1942165},
url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1942165/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Hypothesis-generating network toxicology analysis of potential molecular convergence between a polystyrene oligomer proxy and papillary thyroid carcinoma
AU - Weidong Xie
AU - Jian Tang
AU - Xiaoyu Qian
PY - 2026
DA - 2026/10/14
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.1942165
UR - https://www.frontiersin.org/articles/10.3389/fendo.2026.1942165/full
AB - Background: Polystyrene microplastics (PS-MPs) are emerging environmental contaminants with endocrine-disrupting and pro-inflammatory effects, but whether PS-MPs-associated molecular targets converge with papillary thyroid carcinoma (PTC) alterations remains unclear. This hypothesis-generating study aimed to identify candidate molecular networks and cellular contexts shared between a simplified polystyrene computational proxy and PTC. Methods: Putative targets from CTD and from TargetNet/SwissTargetPrediction using a five-styrene-unit oligomer proxy were intersected with thyroid cancer-related genes from OMIM and GeneCards. Protein functional-association and enrichment analyses were followed by differential expression analysis in GSE33630 (45 normal and 49 PTC samples). LASSO and SVM-RFE identified core genes; stability was examined by repeated nested resampling conditional on the seven-gene candidate panel. Individual-gene tumor-normal discrimination was assessed in GSE33630 and GSE60542. Protein patterns were evaluated qualitatively in the Human Protein Atlas and preliminarily in 15 matched PTC-adjacent tissue pairs. CIBERSORT-estimated immune fractions and two single-cell datasets were analyzed as exploratory context. Results: Among 144 putative proxy-associated targets and 2,139 thyroid cancer-related genes, 75 were shared. Seven candidates overlapped with 1,306 PTC differentially expressed genes, and BCL2, BAX, and FN1 were selected by both feature-selection methods and remained stable across the tested GeneCards thresholds and CTD-only sensitivity analysis. BCL2 was downregulated, whereas BAX and FN1 were upregulated in PTC; individual-gene AUCs were 0.963, 0.941, and 0.965 in GSE33630 and 0.942, 0.907, and 0.955 in GSE60542. HPA images and clinical IHC supported the same protein-level directions. After multiple-testing correction, only the CIBERSORT-estimated neutrophil fraction differed between groups (higher in PTC; q=0.0021). Single-cell analysis localized the three genes across epithelial, stromal, and immune compartments. Conclusion: BCL2, BAX, and FN1 are candidate molecular nodes at the convergence of polystyrene-proxy annotations and PTC-associated alterations. The findings do not demonstrate patient PS-MPs exposure, intact-particle effects, or causality, and require validation in material-characterized exposure experiments and exposure-aware clinical studies.
SN - 1664-2392
ER -