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Jiwen Cheng

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Open access Jul 2026

Environmental exposome study for prostate cancer in elderly men from Western China: preliminary findings from a case–control study in the WeEndPd cohort

Abstract Objectives To investigate the association between exposure to specific endocrine-disrupting chemicals (EDCs), air pollutants and the risk of localised prostate cancer (PCa) and to evaluate the combined effect of mixed EDC exposures. Design A case–control study. Setting Secondary care; a single tertiary hospital in Western China. Participants A total of 580 patients with histologically confirmed localised PCa who underwent radical prostatectomy between May 2021 and June 2023 were included as cases. They were matched 1:2 with 1160 cancer-free controls from the same cohort on age (±5 years) and date of biological sample collection. Key exclusion criteria were a history of other malignancies, androgen deprivation therapy prior to surgery or acute urinary infection. Primary and secondary outcome measures The primary outcome was the odds of PCa associated with individual and mixed exposures. Primary exposures were urinary concentrations of nine bisphenols (BPs) and nine phthalate metabolites (quantified via high-performance liquid chromatography–tandem mass spectrometry) and estimated ambient air pollution exposure (sulphur dioxide (SO2) and PM₂.₅) based on geocoded residential addresses. Results A total of 580 cases and 1160 controls were included in the final analysis. Exposure to the highest quartile of sulphur dioxide (SO2) over 5 years (9.37–28.79 µg/m3) was significantly associated with PCa, yielding an OR of 1.65 (95% CI 1.08 to 2.72; p<0.001) compared with the lowest quartile (3.61–6.89 µg/m3). Urinary concentrations of multiple phthalate metabolites (MECPP, MEHHP and MEHP) and BPs (bisphenol A (BPA) and BPZ) were significantly higher in cases (all p<0.05). Weighted quantile sum (WQS) regression analysis demonstrated a significant positive association between the mixture of EDCs and PCa risk (WQS OR=1.26, 95% CI 1.20 to 1.33; p<0.001). Conclusions Exposure to SO2 and specific EDCs (both individually and as a mixture) is significantly associated with localised PCa. Trial registration number ChiCTR1900024623.

Xianghong Zhou, Yuchong He, Yumin Jin et al. · 0 citations
Open access Jul 2026

Single‐Cell Dissection of Therapy‐Induced Remodeling Uncovers a Fibroblast‐Driven Immunosuppressive Niche and Targetable Vulnerabilities in Lethal Prostate Cancer

ABSTRACT Therapy resistance in prostate cancer arises from coordinated remodeling of malignant and stromal compartments, yet the mechanisms orchestrating this ecosystem adaptation remain elusive. Here, single‐cell RNA sequencing of longitudinal biopsies obtained before and after androgen‐deprivation therapy (ADT) delineated a therapy‐induced stromal lineage bifurcation toward APOD+ and DPT+ fibroblast states. DPT+ fibroblasts activated a C3‐ITGAX/ITGB2 complement signaling axis targeting macrophages, coinciding with suppression of M1 inflammatory programs, amplification of immune‐checkpoint signaling, and a shift of CD8+ T cells from cytotoxic to exhausted phenotypes. Concomitantly, we identified pre‐existing malignant epithelial subpopulations characterized by reduced AR/KLK3 activity and heightened chromosomal instability that preferentially persisted following therapy. Integrative multi‐omic analyses nominated TSPAN1 as a functional effector of castrate resistant prostate cancer (CRPC) and NRXN1 as a regulator of neuroendocrine plasticity through calcium‐dependent signaling programs. Genetic silencing of either gene suppressed proliferation, clonogenicity, migration, and tumor growth, while attenuating neuroendocrine features in vitro and in vivo. Spatial mapping, functional perturbation, and stromal‐epithelial co‐culture experiments mechanistically established a therapy‐induced DPT+ fibroblast‐complement circuit that enforced immune evasion and channels epithelial trajectories toward CRPC or neuroendocrine prostate cancer. Collectively, these findings defined the DPT+‐complement‐macrophage axis as an actionable vulnerability and position TSPAN1 and NRXN1 as therapeutic entry points to disrupt ADT‐driven tumor ecosystem remodeling in prostate cancer.

Yang Chen, Dandan Dong, Jinling Liao et al. · 0 citations