A comprehensive analysis-based study of Di-(2-ethylhexyl) phthalate (DEHP)-Environmental explanation of bladder cancer progression

Fei Lin; Wen-Cai Zheng; Zhi-Bin Ke; Dong-Ning Chen; Yu-Ting Xue; Yun-Zhi Lin; Xiao-Dong Li; Qing-Shui Zheng; Yong Wei; Xue-Yi Xue; Ning Xu

doi:10.1016/j.envpol.2024.125625

A comprehensive analysis-based study of Di-(2-ethylhexyl) phthalate (DEHP)-Environmental explanation of bladder cancer progression

Environ Pollut. 2024 Dec 31:367:125625. doi: 10.1016/j.envpol.2024.125625. Online ahead of print.

Authors

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. Electronic address: [email protected].
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; Fujian Key Laboratory of Precision Medicine for Cancer, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China. Electronic address: [email protected].

PMID: 39746639
DOI: 10.1016/j.envpol.2024.125625

Abstract

Di-(2-ethylhexyl) phthalate (DEHP) is widely utilized as a plasticizer in industrial manufacturing to enhance the durability and flexibility of plastics. Studies have depicted that DEHP exposure may be associated with multiple cancers, including colorectal, liver and prostate cancer. However, the effects and underlying mechanisms of DEHP on bladder cancer progression remain unspecific. In this work, we explored the correlation between DEHP exposure and bladder cancer through comprehensive analysis. A total of 172 differentially expressed DEHP-related genes (DEDRGs) were screened based on the CTD and TCGA database. In addition, a new prognostic model related to DEHP was developed, which had excellent predictive power for bladder cancer prognoses. Molecular docking techniques were employed to assess the binding affinity of mono(2-ethylhexyl) phthalate (MEHP) to crucial proteins. Lastly, both in vitro and in vivo experiments, along with RNA sequencing, were conducted to elucidate the biological roles and mechanisms of MEHP in bladder cancer. Several new insights into the role of DEHP/MEHP in bladder cancer were given in this study, as well as an awareness of the association between environmental toxicants and cancer progression.

Keywords: Bladder cancer; Di-(2-ethylhexyl) phthalate; Molecular docking; Prognosis model.