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

Sílvia Gomes, Bruno Cavadas, Joana Catarina Ferreira, Patrícia Isabel Marques, Catarina Monteiro, Maria Sucena, Catarina Sousa, Luís Vaz Rodrigues, Gilberto Teixeira, Paula Pinto, Tiago Tavares de Abreu, Cristina Bárbara, Júlio Semedo, Leonor Mota, Ana Sofia Carvalho, Rune Matthiesen, Luísa Pereira, Susana Seixas

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Abstract

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.

Original languageEnglish
Article number12838
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019

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Microbiota
Squamous Cell Carcinoma
Adenocarcinoma
Proteobacteria
Lung Neoplasms
Lung
Neoplasms
16S Ribosomal RNA
Atlases
Therapeutic Irrigation
Enterobacteriaceae
Life Expectancy
rRNA Genes
Ecosystem
Carcinogenesis
Smoking
Genome
Bacteria
Survival

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Gomes, S., Cavadas, B., Ferreira, J. C., Marques, P. I., Monteiro, C., Sucena, M., ... Seixas, S. (2019). Profiling of lung microbiota discloses differences in adenocarcinoma and squamous cell carcinoma. Scientific Reports, 9(1), [12838]. https://doi.org/10.1038/s41598-019-49195-w
Gomes, Sílvia ; Cavadas, Bruno ; Ferreira, Joana Catarina ; Marques, Patrícia Isabel ; Monteiro, Catarina ; Sucena, Maria ; Sousa, Catarina ; Vaz Rodrigues, Luís ; Teixeira, Gilberto ; Pinto, Paula ; Tavares de Abreu, Tiago ; Bárbara, Cristina ; Semedo, Júlio ; Mota, Leonor ; Carvalho, Ana Sofia ; Matthiesen, Rune ; Pereira, Luísa ; Seixas, Susana. / Profiling of lung microbiota discloses differences in adenocarcinoma and squamous cell carcinoma. In: Scientific Reports. 2019 ; Vol. 9, No. 1.
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abstract = "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.",
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Gomes, S, Cavadas, B, Ferreira, JC, Marques, PI, Monteiro, C, Sucena, M, Sousa, C, Vaz Rodrigues, L, Teixeira, G, Pinto, P, Tavares de Abreu, T, Bárbara, C, Semedo, J, Mota, L, Carvalho, AS, Matthiesen, R, Pereira, L & Seixas, S 2019, 'Profiling of lung microbiota discloses differences in adenocarcinoma and squamous cell carcinoma' Scientific Reports, vol. 9, no. 1, 12838. https://doi.org/10.1038/s41598-019-49195-w

Profiling of lung microbiota discloses differences in adenocarcinoma and squamous cell carcinoma. / Gomes, Sílvia; Cavadas, Bruno; Ferreira, Joana Catarina; Marques, Patrícia Isabel; Monteiro, Catarina; Sucena, Maria; Sousa, Catarina; Vaz Rodrigues, Luís; Teixeira, Gilberto; Pinto, Paula; Tavares de Abreu, Tiago; Bárbara, Cristina; Semedo, Júlio; Mota, Leonor; Carvalho, Ana Sofia; Matthiesen, Rune; Pereira, Luísa; Seixas, Susana.

In: Scientific Reports, Vol. 9, No. 1, 12838, 01.12.2019.

Research output: Contribution to journalArticle

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AU - Cavadas, Bruno

AU - Ferreira, Joana Catarina

AU - Marques, Patrícia Isabel

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AU - Sucena, Maria

AU - Sousa, Catarina

AU - Vaz Rodrigues, Luís

AU - Teixeira, Gilberto

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AU - Tavares de Abreu, Tiago

AU - Bárbara, Cristina

AU - Semedo, Júlio

AU - Mota, Leonor

AU - Carvalho, Ana Sofia

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AU - Seixas, Susana

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N2 - 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.

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