关键词: adrenocortical carcinoma intratumoral microbiota microbiome prognosis

来  源:   DOI:10.1002/imt2.102   PDF(Pubmed)

Abstract:
Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy. Recent studies have discovered a pivotal role of the intratumoral microbiota in various cancers, yet it remains elusive in ACC. Here, we explored the intratumoral microbiome data derived from in silico identification, further validated in an in-house cohort by bacterial 16S rRNA fluorescence in situ hybridization and lipopolysaccharide staining. Unsupervised clustering determined two naturally distinct clusters of the intratumoral microbiome in ACC, which was associated with overall survival. The incorporation of microbial signatures enhanced the prognostic performance of the clinical stage in an immunity-dependent manner. Genetic and transcriptomic association analyses identified significant upregulation of the cell cycle and p53 signaling pathways associated with microbial signatures for worsened prognosis. Our study not only supports the presence of intratumoral bacteria but also implies a prognostic and biological role of intratumoral microbiota in ACC, which can advance a better understanding of the biology of ACC.
摘要:
肾上腺皮质癌(ACC)是一种罕见但侵袭性的恶性肿瘤。最近的研究发现肿瘤内微生物在各种癌症中的关键作用,然而,它在ACC中仍然难以捉摸。这里,我们探索了来自计算机识别的肿瘤内微生物组数据,通过细菌16SrRNA荧光原位杂交和脂多糖染色在内部队列中进一步验证。无监督聚类确定了ACC中瘤内微生物组的两个自然不同的聚类,这与总生存率有关。微生物特征的掺入以免疫依赖性方式增强了临床阶段的预后性能。遗传和转录组关联分析确定了与微生物特征相关的细胞周期和p53信号通路的显着上调,以导致预后恶化。我们的研究不仅支持肿瘤内细菌的存在,而且还暗示了肿瘤内微生物在ACC中的预后和生物学作用。这可以促进对ACC生物学的更好理解。
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