Profiling of lung microbiota discloses differences in adenocarcinoma and squamous cell carcinoma

Profiling of lung microbiota discloses differences in adenocarcinoma and squamous cell carcinoma
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DOI:
10.1038/s41598-019-49195-w
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发表时间:
2019-09-06
期刊:
影响因子:
4.6
通讯作者:
Seixas, Susana
Seixas, Susana
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Gomes, Silvia;Cavadas, Bruno;Seixas, Susana

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肺是一个由宿主细胞和微生物组成的复杂生态系统,在病理状态下经常被破坏。虽然细菌被假设为致癌的媒介,但对最常见的癌症亚型:腺癌(ADC)和鳞状细胞癌(SCC)的微生物群特征知之甚少。为了表征肺癌(LC)微生物群,首先使用103个支气管肺泡灌洗液样本,通过16S核糖体RNA基因(V3-V6)的混合测序方法进行筛选。然后,鉴定出的分类群用于检查来自癌症基因组图谱的1009例病例,并注释肿瘤未映射的RNAseq reads。根据癌症亚型、吸烟史和气流阻塞等临床数据分析微生物多样性。我们发现LC微生物群在变形菌门中丰富,在SCC中比ADC更多样化,特别是在男性和重度吸烟者中。Proteobacteria的高频率被发现区分了一个主要的集群,进一步细分为与ADC或SCC相关的定义明确的群落。在这里,SCC亚群与其他病例的不同之处在于生存率较差与几种肠杆菌科相关。总的来说,这项研究为肺部微生物群与癌症亚型之间的相关性及其对患者预期寿命的影响提供了第一个证据。
The lung is a complex ecosystem of host cells and microbes often disrupted in pathological conditions. Although bacteria have been hypothesized as agents of carcinogenesis, little is known about microbiota profile of the most prevalent cancer subtypes: adenocarcinoma (ADC) and squamous cell carcinoma (SCC). To characterize lung cancer (LC) microbiota a first a screening was performed through a pooled sequencing approach of 16S ribosomal RNA gene (V3-V6) using a total of 103 bronchoalveaolar lavage fluid samples. Then, identified taxa were used to inspect 1009 cases from The Cancer Genome Atlas and to annotate tumor unmapped RNAseq reads. Microbial diversity was analyzed per cancer subtype, history of cigarette smoking and airflow obstruction, among other clinical data. We show that LC microbiota is enriched in Proteobacteria and more diverse in SCC than ADC, particularly in males and heavier smokers. High frequencies of Proteobacteria were found to discriminate a major cluster, further subdivided into well-defined communities' associated with either ADC or SCC. Here, a SCC subcluster differing from other cases by a worse survival was correlated with several Enterobacteriaceae. Overall, this study provides first evidence for a correlation between lung microbiota and cancer subtype and for its influence on patient life expectancy.