2. Academic Validation
  3. Integrative analysis of DEHP exposure and prostate cancer: Mechanistic insights and predictive modeling

Integrative analysis of DEHP exposure and prostate cancer: Mechanistic insights and predictive modeling

  • Environ Pollut. 2026 Mar 1:392:127628. doi: 10.1016/j.envpol.2025.127628.
Wen-Cai Zheng 1,  Wen-Tao Xu 1,  Chao-Ran Chen 1,  Fei Lin 1,  Shao-Hao Chen 1,  Xiao-Dong Li 1,  Xiong-Lin Sun 1,  Qing-Shui Zheng 1,  Yong Wei 1,  Xue-Yi Xue 2,  Zhi-Bin Ke 3,  Ning Xu 4
Affiliations

Affiliations

  • 1 Department of Urology, Urology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China; Department of Urology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China.
  • 2 Department of Urology, Urology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China; Department of Urology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China; Fujian Key Laboratory of Precision Medicine for Cancer, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.
  • 3 Department of Urology, Urology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China; Department of Urology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China. Electronic address: [email protected].
  • 4 Department of Urology, Urology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China; Department of Urology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China; Fujian Key Laboratory of Precision Medicine for Cancer, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China. Electronic address: [email protected].
PMID: 41483848 DOI: 10.1016/j.envpol.2025.127628
Abstract

Objective: Di-(2-ethylhexyl) phthalate (DEHP), a ubiquitous plasticizer of significant health concern due to its endocrine disrupting effects. The study aims to elucidate underlying molecular mechanisms between DEHP exposure and prostate Cancer (PCa).

Methods: In vitro and in vivo experiments were undertaken to validate the effects of DEHP on the biological function of prostate Cancer, and RNA Sequencing was performed to elucidate the underlying mechanism. We integrated in silico toxicological assessments and bioinformatics methodologies was employed to investigate the key targets and associated downstream pathways in DEHP-induced PCa progression.

Results: In vitro and in vivo experiments showed that MEHP promoted the proliferation, migration, and invasion of PCa cells and tumorigenicity, and RNA Sequencing revealed that the metabolic pathways, pathways in Cancer, PI3K-Akt signaling pathway, MAPK signaling pathway might be potential mechanisms involved in this process. Additionally, six DEHP-related genes were identified and a DEHP-related model was constructed. The data of scRNA indicated that these six DEHP-related genes may contribute in the tumor microenvironment of PCa. The molecular docking analysis revealed DEHP's ability to bind to crucial DEHP -related proteins.

Conclusions: Our study unveils a novel insight into the function for DEHP in PCa, shedding new light on prediction, assessment, and mitigation of DEHP exposure and PCa progression.

Keywords

Biochemical recurrence; Di-(2-ethylhexyl) phthalate; Molecular docking; Progression; Prostate cancer.

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