1 Division of Pulmonary and Critical Care Medicine.
2 Flatiron Institute, Center for Computational Biology, Simons Foundation, New York, New York.
Am J Respir Crit Care Med. 2018 Nov 1;198(9):1188-1198. doi: 10.1164/rccm.201710-2118OC.
In lung cancer, upregulation of the PI3K (phosphoinositide 3-kinase) pathway is an early event that contributes to cell proliferation, survival, and tissue invasion. Upregulation of this pathway was recently described as associated with enrichment of the lower airways with bacteria identified as oral commensals.
We hypothesize that host-microbe interactions in the lower airways of subjects with lung cancer affect known cancer pathways.
Airway brushings were collected prospectively from subjects with lung nodules at time of diagnostic bronchoscopy, including 39 subjects with final lung cancer diagnoses and 36 subjects with noncancer diagnoses. In addition, samples from 10 healthy control subjects were included. 16S ribosomal RNA gene amplicon sequencing and paired transcriptome sequencing were performed on all airway samples. In addition, an in vitro model with airway epithelial cells exposed to bacteria/bacterial products was performed.
The composition of the lower airway transcriptome in the patients with cancer was significantly different from the control subjects, which included up-regulation of ERK (extracellular signal-regulated kinase) and PI3K signaling pathways. The lower airways of patients with lung cancer were enriched for oral taxa (Streptococcus and Veillonella), which was associated with up-regulation of the ERK and PI3K signaling pathways. In vitro exposure of airway epithelial cells to Veillonella, Prevotella, and Streptococcus led to upregulation of these same signaling pathways.
The data presented here show that several transcriptomic signatures previously identified as relevant to lung cancer pathogenesis are associated with enrichment of the lower airway microbiota with oral commensals.
在肺癌中，PI3K（磷酸肌醇 3-激酶）途径的上调是导致细胞增殖、存活和组织侵袭的早期事件。最近有研究表明，该途径的上调与富含被鉴定为口腔共生菌的下气道有关。
我们假设肺癌患者下气道中的宿主-微生物相互作用会影响已知的癌症途径。
前瞻性地从诊断性支气管镜检查时患有肺结节的患者中收集气道刷检标本，包括 39 例最终诊断为肺癌的患者和 36 例非癌症诊断的患者。此外，还纳入了 10 例健康对照者的样本。对所有气道样本进行 16S 核糖体 RNA 基因扩增子测序和配对转录组测序。此外，还进行了气道上皮细胞暴露于细菌/细菌产物的体外模型实验。
癌症患者下气道转录组的组成与对照组有显著差异，包括 ERK（细胞外信号调节激酶）和 PI3K 信号通路的上调。肺癌患者的下气道富含口腔分类群（链球菌和韦荣球菌），这与 ERK 和 PI3K 信号通路的上调有关。体外暴露于气道上皮细胞的韦荣球菌、普雷沃氏菌和链球菌导致这些相同的信号通路上调。
本文提供的数据表明，先前被认为与肺癌发病机制相关的几个转录组特征与富含口腔共生菌的下气道微生物群有关。
