背景:肝细胞癌(HCC)在肿瘤学中仍然是一个巨大的挑战,其发病机制和进展受多种因素影响。其中,无处不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,被推测发挥作用。本研究试图阐明双酚A之间复杂的相互作用,肝癌的免疫微环境,以及这种恶性肿瘤的更广泛的分子景观。
方法:使用来自癌症基因组图谱和比较毒性基因组学数据库的数据进行综合分析。进行严格的差异表达分析,补充基因本体论和京都百科全书的基因和基因组富集分析。此外,单样本基因集富集分析,采用基因集富集分析和基因集变异分析来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。
结果:我们的发现揭示了HCC中活跃的免疫细胞和功能的多样性。高免疫相关分数之间出现了明显的相关性,建立了肿瘤微环境的标志物和免疫检查点基因的表达。一个重要的发现是鉴定了与免疫相关途径和BPA暴露同时相关的关键基因。利用这些基因,制作了一个预后模型,提供对HCC患者预后的预测性见解。有趣的是,体外研究表明,BPA暴露可以促进肝癌细胞的增殖。
结论:这项研究强调了HCC免疫微环境的多面性,并阐明了BPA的潜在调节作用。构建的预后模型,如果进一步验证,可以作为肝癌风险分层的有力工具,潜在的指导治疗策略。此外,这些发现对免疫疗法的影响是深远的,提出了提高治疗效果的新途径。随着与HCC的战斗继续,对像BPA这样的环境调节剂的理解变得越来越重要。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.