Exploring the interplay between bisphenol A exposure, the immune microenvironment and hepatocellular carcinoma progression

IF 3.2 4区 医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Qi Liu, Ruishu Niu, Yi Ye, Jie Li
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引用次数: 0

Abstract

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.

Conclusion

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.

Abstract Image

探索双酚 A 暴露、免疫微环境与肝细胞癌进展之间的相互作用。
背景:肝细胞癌(HCC)仍然是肿瘤学中的一项艰巨挑战,其发病机制和进展受多种因素的影响。其中,普遍存在的有机合成化合物双酚 A(BPA)曾与各种不良健康影响有关,人们推测它在其中发挥了作用。本研究试图阐明双酚 A、HCC 的免疫微环境以及这种恶性肿瘤更广泛的分子环境之间复杂的相互作用:利用从癌症基因组图谱(The Cancer Genome Atlas)和比较毒物基因组学数据库(Comparative Toxicogenomics Database)获得的数据进行了全面分析。进行了严格的差异表达分析,并辅以基因本体和京都基因和基因组百科全书的富集分析。此外,还采用了单样本基因组富集分析、基因组富集分析和基因组变异分析,以揭示潜在的分子联系和见解。对免疫浸润模式进行了描述,并对 HCC 细胞进行了一系列体外实验,以直接评估双酚 A 暴露的影响:结果:我们的研究结果揭示了 HCC 中活跃的免疫细胞和功能的多样性。高免疫相关评分、肿瘤微环境的既定标记物和免疫检查点基因的表达之间存在明显的相关性。一项重大发现是确定了与免疫相关途径和双酚 A 暴露同时相关的关键基因。利用这些基因建立了一个预后模型,为预测 HCC 患者的预后提供了洞察力。有趣的是,体外研究表明,暴露于双酚 A 可促进 HCC 细胞的增殖:这项研究强调了 HCC 免疫微环境的多面性,并揭示了双酚 A 在其中的潜在调节作用。所构建的预后模型如能得到进一步验证,将成为对 HCC 进行风险分层的有力工具,并有可能为治疗策略提供指导。此外,这些发现对免疫疗法也有深远的影响,为提高疗效提供了新的途径。随着与 HCC 斗争的继续,对双酚 A 等环境调节剂的了解变得越来越重要。
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来源期刊
Journal of Gene Medicine
Journal of Gene Medicine 医学-生物工程与应用微生物
CiteScore
6.40
自引率
0.00%
发文量
80
审稿时长
6-12 weeks
期刊介绍: The aims and scope of The Journal of Gene Medicine include cutting-edge science of gene transfer and its applications in gene and cell therapy, genome editing with precision nucleases, epigenetic modifications of host genome by small molecules, siRNA, microRNA and other noncoding RNAs as therapeutic gene-modulating agents or targets, biomarkers for precision medicine, and gene-based prognostic/diagnostic studies. Key areas of interest are the design of novel synthetic and viral vectors, novel therapeutic nucleic acids such as mRNA, modified microRNAs and siRNAs, antagomirs, aptamers, antisense and exon-skipping agents, refined genome editing tools using nucleic acid /protein combinations, physically or biologically targeted delivery and gene modulation, ex vivo or in vivo pharmacological studies including animal models, and human clinical trials. Papers presenting research into the mechanisms underlying transfer and action of gene medicines, the application of the new technologies for stem cell modification or nucleic acid based vaccines, the identification of new genetic or epigenetic variations as biomarkers to direct precision medicine, and the preclinical/clinical development of gene/expression signatures indicative of diagnosis or predictive of prognosis are also encouraged.
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