A pan-cancer mycobiome analysis reveals fungal involvement in gastrointestinal and lung tumors.

A pan-cancer mycobiome analysis reveals fungal involvement in gastrointestinal and lung tumors.
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DOI:
10.1016/j.cell.2022.09.015
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发表时间:
2022-09-29
期刊:
影响因子:
64.5
通讯作者:
Iliev, Iliyan D.
Iliev, Iliyan D.
中科院分区:
生物学1区
文献类型:
--
作者:
Dohlman, Anders B.;Klug, Jared;Mesko, Marissa;Gao, Iris H.;Lipkin, Steven M.;Shen, Xiling;Iliev, Iliyan D.

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真菌微生物群(mycobiota)是人类微生物群中一个很小但具有免疫反应性的组成部分,但人们对它们在人类癌症中的作用知之甚少。对多个身体部位的泛癌症分析显示,每104个肿瘤细胞中有多达1个真菌。在肺癌中,芽生菌与肿瘤组织相关。在胃癌中,念珠菌的高发率与促炎免疫途径的表达有关,而在结肠癌中,念珠菌可预测转移性疾病和细胞粘连减弱。在多个胃肠道部位,活的念珠菌种类在肿瘤样本中富集,肿瘤相关的念珠菌DNA可预测生存率降低。通过肿瘤样本的外部ITS测序和独立队列的培养依赖分析,证实了念珠菌在人类胃肠道肿瘤中的存在。这些数据暗示了真菌菌群在胃肠道癌症发病机制中的作用,并提示肿瘤相关的真菌DNA可能作为诊断或预后的生物标志物。
Fungal microorganisms (mycobiota) comprise a small but immunoreactive component of the human microbiome, yet little is known about their role in human cancers. Pan-cancer analysis of multiple body sites revealed tumor-specific mycobiomes at up to 1 fungal per 104 tumor cells. In lung cancer, Blastomyces was associated with tumor tissues. In stomach cancers, high rates of Candida were linked to the expression of proinflammatory immune pathways, while in colon cancers Candida was predictive of metastatic disease and attenuated cellular adhesions. Across multiple GI sites, live Candida species were enriched in tumor samples and tumor-associated Candida DNA was predictive of decreased survival. The presence of Candida in human GI tumors was confirmed by external ITS sequencing of tumor samples and by culture-dependent analysis in an independent cohort. These data implicate the mycobiota in the pathogenesis of GI cancers and suggest that tumor-associated fungal DNA may serve as diagnostic or prognostic biomarkers.
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