Huaian Hospital of Huaian City, Huaian, China.
Jiangsu University, Zhenjiang, China.
J Gene Med. 2024 Sep;26(9):e3723. doi: 10.1002/jgm.3723.
Hepatocellular carcinoma (HCC) remains a formidable challenge in oncology, with its pathogenesis and progression influenced by myriad factors. Among them, the pervasive organic synthetic compound, bisphenol A (BPA), previously linked with various adverse health effects, has been speculated to play a role. This study endeavors to elucidate the complex interplay between BPA, the immune microenvironment of HCC, and the broader molecular landscape of this malignancy.
A comprehensive analysis was undertaken using data procured from both The Cancer Genome Atlas and the Comparative Toxicogenomics Database. Rigorous differential expression analyses were executed, supplemented by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. In addition, single-sample gene set enrichment analysis, gene set enrichment analysis and gene set variation analysis were employed to reveal potential molecular links and insights. Immune infiltration patterns were delineated, and a series of in vitro experiments on HCC cells were conducted to directly assess the impact of BPA exposure.
Our findings unveiled a diverse array of active immune cells and functions within HCC. Distinct correlations emerged between high-immune-related scores, established markers of the tumor microenvironment and the expression of immune checkpoint genes. A significant discovery was the identification of key genes simultaneously associated with immune-related pathways and BPA exposure. Leveraging these genes, a prognostic model was crafted, offering predictive insights into HCC patient outcomes. Intriguingly, in vitro studies suggested that BPA exposure could promote proliferation in HCC cells.
This research underscores the multifaceted nature of HCC's immune microenvironment and sheds light on BPA's potential modulatory effects therein. The constructed prognostic model, if validated further, could serve as a robust tool for risk stratification in HCC, potentially guiding therapeutic strategies. Furthermore, the implications of the findings for immunotherapy are profound, suggesting new avenues for enhancing treatment efficacy. As the battle against HCC continues, understanding of environmental modulators like BPA becomes increasingly pivotal.
肝细胞癌（HCC）仍然是肿瘤学领域的一个严峻挑战，其发病机制和进展受到众多因素的影响。其中，普遍存在的有机合成化合物双酚 A（BPA）以前与各种不良健康影响有关，据推测它在其中发挥作用。本研究旨在阐明 BPA、HCC 的免疫微环境以及这种恶性肿瘤更广泛的分子特征之间的复杂相互作用。
使用从癌症基因组图谱和比较毒理学基因组数据库中获取的数据进行了全面分析。进行了严格的差异表达分析，并补充了基因本体论和京都基因与基因组百科全书富集分析。此外，还进行了单样本基因集富集分析、基因集富集分析和基因集变异分析，以揭示潜在的分子联系和见解。描绘了免疫浸润模式，并对 HCC 细胞进行了一系列体外实验，以直接评估 BPA 暴露的影响。
我们的研究结果揭示了 HCC 中多样化的活跃免疫细胞和功能。高免疫相关评分与肿瘤微环境的既定标志物以及免疫检查点基因的表达之间存在明显的相关性。一个重要的发现是确定了同时与免疫相关途径和 BPA 暴露相关的关键基因。利用这些基因，构建了一个预后模型，为 HCC 患者的预后提供了预测性见解。有趣的是，体外研究表明 BPA 暴露可以促进 HCC 细胞的增殖。
这项研究强调了 HCC 免疫微环境的多面性质，并揭示了 BPA 在此中的潜在调节作用。如果进一步验证，构建的预后模型可以作为 HCC 风险分层的强大工具，可能指导治疗策略。此外，这些发现对免疫疗法的意义深远，为提高治疗效果提供了新途径。随着对 HCC 的持续斗争，对 BPA 等环境调节剂的理解变得越来越重要。
