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肝癌及癌旁正常组织中阶段依赖的微生物动态变化。

Stage dependent microbial dynamics in hepatocellular carcinoma and adjacent normal liver tissues.

机构信息

Technology Innovation Research Division, World Institute of Kimchi, Gwangju, 61755, Republic of Korea.

Department of Biomedical Sciences and Department of Microbiology, Chonnam National University Medical School, Gwangju, 61469, Republic of Korea.

出版信息

Sci Rep. 2024 Oct 30;14(1):26092. doi: 10.1038/s41598-024-77260-6.

DOI:10.1038/s41598-024-77260-6
PMID:39478014
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11525880/
Abstract

The interactive pathway of the gut-liver axis underscores the significance of microbiome modulation in the pathogenesis and progression of various liver diseases, including hepatocellular carcinoma (HCC). This study aims to investigate the disparities in the composition and functionality of the hepatic microbiota between tumor tissues and adjacent normal liver tissues, and their implications in the etiology of HCC. We conducted a comparative analysis of the hepatic microbiome between adjacent normal liver tissues and tumor tissues from HCC patients. Samples were categorized according to the modified Union for International Cancer Control (mUICC) staging system into Non-tumor, mUICC stage I, mUICC stage II, and mUICC stage III groups. Microbial richness and community composition were analyzed, and phylogenetic profiles were examined to identify significantly altered microbial taxa among the groups. Predicted metabolic pathways were analyzed using PICRUSt2. Our analysis did not reveal significant differences in microbial richness and community composition with the development of HCC. However, phylogenetic profiling identified significantly altered microbial taxa among the groups. Sphingobium, known for degrading polychlorinated biphenyls (PCBs), exhibited a significantly negative correlation with clinical indices in HCC patients. Conversely, Sphingomonas, a gut bacterium associated with various liver diseases, showed a positive correlation. Predicted metabolic pathways suggested a correlation between atrazine degradation and valine, leucine, and isoleucine biosynthesis with mUICC stage and tumor size. Our results underscore the critical link between hepatic microbial composition and function and the HCC tumor stage, suggesting a potentially pivotal role in the development of HCC. These findings highlight the importance of targeting the hepatic microbiome for therapeutic strategies in HCC.

摘要

肠道-肝脏轴的相互作用途径强调了微生物组调节在各种肝脏疾病(包括肝细胞癌[HCC])发病机制和进展中的重要性。本研究旨在探讨肿瘤组织和相邻正常肝组织之间肝微生物组的组成和功能差异,以及它们在 HCC 发病机制中的意义。我们对 HCC 患者的相邻正常肝组织和肿瘤组织的肝微生物组进行了比较分析。根据改良的国际癌症控制联盟(mUICC)分期系统,将样本分为非肿瘤、mUICC Ⅰ期、mUICC Ⅱ期和 mUICC Ⅲ期组。分析了微生物丰富度和群落组成,并检查了系统发育图谱,以确定各组中明显改变的微生物类群。使用 PICRUSt2 分析了预测的代谢途径。我们的分析没有发现随着 HCC 的发展,微生物丰富度和群落组成有显著差异。然而,系统发育分析确定了各组中明显改变的微生物类群。 Sphingobium 以降解多氯联苯(PCBs)而闻名,其在 HCC 患者的临床指标中呈显著负相关。相反,与各种肝脏疾病相关的肠道细菌 Sphingomonas 呈正相关。预测的代谢途径表明,莠去津降解与 mUICC 分期和肿瘤大小与缬氨酸、亮氨酸和异亮氨酸生物合成之间存在相关性。我们的研究结果强调了肝微生物组成和功能与 HCC 肿瘤分期之间的关键联系,提示其在 HCC 发生发展中可能具有重要作用。这些发现突出了针对肝微生物组的治疗策略在 HCC 中的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e216/11525880/0a8245a4afd0/41598_2024_77260_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e216/11525880/ad7a0882f553/41598_2024_77260_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e216/11525880/649012d847e9/41598_2024_77260_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e216/11525880/00cb70de160f/41598_2024_77260_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e216/11525880/c1284adbf241/41598_2024_77260_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e216/11525880/e90b23689f1f/41598_2024_77260_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e216/11525880/0a8245a4afd0/41598_2024_77260_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e216/11525880/ad7a0882f553/41598_2024_77260_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e216/11525880/649012d847e9/41598_2024_77260_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e216/11525880/00cb70de160f/41598_2024_77260_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e216/11525880/c1284adbf241/41598_2024_77260_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e216/11525880/e90b23689f1f/41598_2024_77260_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e216/11525880/0a8245a4afd0/41598_2024_77260_Fig6_HTML.jpg

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