Zhang Xiaolei, Huang Wen, Huang Tao, Zhang Jiayi, Xu Aiming, Cheng Yidong, Qin Chao, Lu Qiang, Wang Zengjun
Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Good Clinical Practice (GCP) Office, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Front Oncol. 2023 Oct 5;13:1260114. doi: 10.3389/fonc.2023.1260114. eCollection 2023.
In recent years, organophosphate ester flame retardants (OPFRs) have emerged as preferred alternatives to brominated flame retardants (BFRs) in materials such as building supplies, textiles, and furnishings. Simultaneously, a notable surge in bladder cancer incidences has been observed globally, particularly in developed nations, placing it as the 10th most prevalent cancer type. Among the extensive OPFRs, the linkage between triphenyl phosphate (TPP) and bladder cancer remains inadequately investigated. Hence, our study endeavors to elucidate this potential association. We sourced transcriptome profiles and TPP-related data from The Cancer Genome Atlas and Comparative Toxicogenomics databases. Using the ssGSEA algorithm, we established TPP-correlated scores within the bladder cancer cohort. Differentially expressed analysis enabled us to identify key genes in bladder cancer patients. We utilized the LASSO regression analysis, along with univariate and multivariate COX regression analyses to construct a prognostic prediction model. To uncover critical pathways involving key genes, we employed GSEA and GSVA enrichment analyses. Molecular docking analysis was performed to determine the binding capability between TPP and proteins. Our findings reveal that the TPP-centric risk model offers valuable prediction for bladder cancer cohorts. Furthermore, the reliability of this TPP-influenced risk model was verified through ROC curve analysis and survival studies. Intriguingly, TPP exposure appears to bolster the proliferation and invasiveness of bladder cancer cells. This study furnishes new insights into the possible benefits of minimizing TPP exposure for hindering bladder cancer progression.
近年来，有机磷酸酯类阻燃剂（OPFRs）已成为建筑材料、纺织品和家具等材料中溴化阻燃剂（BFRs）的首选替代品。与此同时，全球范围内膀胱癌发病率显著上升，尤其是在发达国家，使其成为第10大最常见的癌症类型。在众多的OPFRs中，磷酸三苯酯（TPP）与膀胱癌之间的联系仍未得到充分研究。因此，我们的研究致力于阐明这种潜在关联。我们从癌症基因组图谱和比较毒理基因组学数据库中获取了转录组图谱和与TPP相关的数据。使用单样本基因集富集分析（ssGSEA）算法，我们在膀胱癌队列中建立了与TPP相关的评分。差异表达分析使我们能够识别膀胱癌患者中的关键基因。我们利用套索回归分析以及单变量和多变量COX回归分析来构建预后预测模型。为了揭示涉及关键基因的关键通路，我们进行了基因集富集分析（GSEA）和基因集变异分析（GSVA）。进行分子对接分析以确定TPP与蛋白质之间的结合能力。我们的研究结果表明，以TPP为中心的风险模型为膀胱癌队列提供了有价值的预测。此外，通过ROC曲线分析和生存研究验证了这种受TPP影响的风险模型的可靠性。有趣的是，TPP暴露似乎会增强膀胱癌细胞的增殖和侵袭性。这项研究为减少TPP暴露以阻碍膀胱癌进展的潜在益处提供了新的见解。
