Network toxicological insights into DEHP exposure and thyroid cancer development and progression

This study aimed to identify markers of di-2-ethylhexyl phthalate (DEHP) exposure associated with thyroid cancer occurrence and prognosis by integrating network toxicology and molecular docking. Expression profiles and clinical information were obtained from TCGA-THCA and five GEO datasets (GSE3467,...

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Main Authors: Yuhang Zhang, Qiang Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1617202/full
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author Yuhang Zhang
Qiang Wang
author_facet Yuhang Zhang
Qiang Wang
author_sort Yuhang Zhang
collection DOAJ
description This study aimed to identify markers of di-2-ethylhexyl phthalate (DEHP) exposure associated with thyroid cancer occurrence and prognosis by integrating network toxicology and molecular docking. Expression profiles and clinical information were obtained from TCGA-THCA and five GEO datasets (GSE3467, GSE3678, GSE33630, GSE53157, and GSE60542). Venn diagram analysis revealed six overlapping genes (CYP1B1, ABCC3, KRT19, CUX2, GABRB2, and TNFSF15) between the combined dataset and DEHP’s target genes. GO and KEGG enrichment analyses were conducted on these overlapping genes. Through multivariate COX regression model, it is clearly seen that CYP1B1, GABRB2 and TNFSF15 are highly expressed, and can basically be determined as candidate hub genes. Kaplan-Meier survival analysis indicated that the high-risk group had a significantly poorer prognosis (p < 0.05). Furthermore, prognostic ROC curves based on the GEO validation set demonstrated that CYP1B1, GABRB2, and TNFSF15 were significantly associated with thyroid cancer diagnosis (AUC exceeding 0.86). Finally, molecular docking was employed to visualize the interaction sites between DEHP and its target genes. In conclusion, this study provides novel targets for the prevention and treatment of thyroid cancer in the context of DEHP exposure.
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spelling doaj-art-1852282b6e3a496f9115c6f2d07687a12025-08-20T04:02:50ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-08-011510.3389/fonc.2025.16172021617202Network toxicological insights into DEHP exposure and thyroid cancer development and progressionYuhang ZhangQiang WangThis study aimed to identify markers of di-2-ethylhexyl phthalate (DEHP) exposure associated with thyroid cancer occurrence and prognosis by integrating network toxicology and molecular docking. Expression profiles and clinical information were obtained from TCGA-THCA and five GEO datasets (GSE3467, GSE3678, GSE33630, GSE53157, and GSE60542). Venn diagram analysis revealed six overlapping genes (CYP1B1, ABCC3, KRT19, CUX2, GABRB2, and TNFSF15) between the combined dataset and DEHP’s target genes. GO and KEGG enrichment analyses were conducted on these overlapping genes. Through multivariate COX regression model, it is clearly seen that CYP1B1, GABRB2 and TNFSF15 are highly expressed, and can basically be determined as candidate hub genes. Kaplan-Meier survival analysis indicated that the high-risk group had a significantly poorer prognosis (p < 0.05). Furthermore, prognostic ROC curves based on the GEO validation set demonstrated that CYP1B1, GABRB2, and TNFSF15 were significantly associated with thyroid cancer diagnosis (AUC exceeding 0.86). Finally, molecular docking was employed to visualize the interaction sites between DEHP and its target genes. In conclusion, this study provides novel targets for the prevention and treatment of thyroid cancer in the context of DEHP exposure.https://www.frontiersin.org/articles/10.3389/fonc.2025.1617202/fullDEHPnetwork toxicologicalthyroid cancerTCGAGEO
spellingShingle Yuhang Zhang
Qiang Wang
Network toxicological insights into DEHP exposure and thyroid cancer development and progression
Frontiers in Oncology
DEHP
network toxicological
thyroid cancer
TCGA
GEO
title Network toxicological insights into DEHP exposure and thyroid cancer development and progression
title_full Network toxicological insights into DEHP exposure and thyroid cancer development and progression
title_fullStr Network toxicological insights into DEHP exposure and thyroid cancer development and progression
title_full_unstemmed Network toxicological insights into DEHP exposure and thyroid cancer development and progression
title_short Network toxicological insights into DEHP exposure and thyroid cancer development and progression
title_sort network toxicological insights into dehp exposure and thyroid cancer development and progression
topic DEHP
network toxicological
thyroid cancer
TCGA
GEO
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1617202/full
work_keys_str_mv AT yuhangzhang networktoxicologicalinsightsintodehpexposureandthyroidcancerdevelopmentandprogression
AT qiangwang networktoxicologicalinsightsintodehpexposureandthyroidcancerdevelopmentandprogression