Shiyao Liao, Yao Kang, Jun Lv, Yichen Lin, Tingxiao Zhao, Longtao Yao, Hong Zhou, Kai Zhou
Center for Plastic & Reconstructive Surgery, Department of Orthopedics, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
Cancer Center, Department of Orthopedics, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
Discov Oncol. 2024 Sep 4;15(1):404. doi: 10.1007/s12672-024-01280-x.
Bisphenol A (BPA) is a common environmental pollutant, and its specific mechanisms in cancer development and its impact on the tumor immune microenvironment are not yet fully understood.
Transcriptome data from osteosarcoma (OS) patients were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. BPA-related genes were identified through the Comparative Toxicogenomics Database (CTD), yielding 177 genes. Differentially expressed genes were analyzed using the GSE162454 dataset from the Tumor Immune Single Cell Hub 2 (TISCH2). We constructed the prognostic model using univariate Cox regression and LASSO analysis. The model was validated using the GSE16091 dataset. GO, KEGG, and GSEA analyses were performed to investigate the mechanisms of BPA-related genes.
A total of 15 BPA-related genes were identified as differentially expressed in OS. Univariate Cox regression and LASSO analysis identified four key prognostic genes (FOLR1, MYC, ESRRA, VEGFA). The prognostic model exhibited strong predictive performance with area under the curve (AUC) values of 0.89, 0.6, and 0.79 for predicting 1-, 2-, and 3-year survival, respectively. External validation using the GSE16091 dataset confirmed the model's high accuracy with AUC values exceeding 0.88. Our results indicated that the prognosis of the high-risk population is generally poorer, which may be associated with alterations in the tumor immune microenvironment. In the high-risk group, immune cells showed predominantly low expression levels, while immune checkpoint genes were significantly overexpressed, along with markedly elevated tumor purity. These findings revealed a correlation between upregulation of BPA-related genes and formation of an immunosuppressive microenvironment, leading to unfavorable patient outcomes.
Our study highlighted the significant association of BPA with OS biology, particularly in its potential role in modulating the tumor immune microenvironment. We offered a fresh insight into the influence of BPA on cancer development, thus providing valuable insights for future clinical interventions and treatment strategies.
双酚A（BPA）是一种常见的环境污染物，其在癌症发生发展中的具体机制及其对肿瘤免疫微环境的影响尚未完全明确。
从治疗应用研究以生成有效治疗方法（TARGET）数据库下载骨肉瘤（OS）患者的转录组数据。通过比较毒理基因组学数据库（CTD）鉴定与BPA相关的基因，共得到177个基因。使用来自肿瘤免疫单细胞中心2（TISCH2）的GSE162454数据集分析差异表达基因。我们使用单变量Cox回归和LASSO分析构建预后模型。使用GSE16091数据集对该模型进行验证。进行基因本体（GO）、京都基因与基因组百科全书（KEGG）和基因集富集分析（GSEA）以研究与BPA相关基因的机制。
共鉴定出15个在骨肉瘤中差异表达的与BPA相关的基因。单变量Cox回归和LASSO分析确定了四个关键的预后基因（FOLR1、MYC、ESRRA、VEGFA）。该预后模型表现出强大的预测性能，预测1年、2年和3年生存率的曲线下面积（AUC）值分别为0.89、0.6和0.79。使用GSE16091数据集进行的外部验证证实了该模型的高准确性，AUC值超过0.88。我们的结果表明，高危人群的预后通常较差，这可能与肿瘤免疫微环境的改变有关。在高危组中，免疫细胞主要表现为低表达水平，而免疫检查点基因显著过表达，同时肿瘤纯度明显升高。这些发现揭示了与BPA相关基因的上调与免疫抑制微环境形成之间的相关性，导致患者预后不良。
我们的研究强调了BPA与骨肉瘤生物学的显著关联，特别是其在调节肿瘤免疫微环境中的潜在作用。我们为BPA对癌症发展的影响提供了新的见解，从而为未来的临床干预和治疗策略提供了有价值的见解。
