Microbiota profile of Non-small Cell Lung Cancer (NSCLC): the study of a large cohort

Abstract

The lung is a complex ecosystem of host cells and microbes often disrupted in airway disorders, such as chronic obstructive pulmonary disease (COPD). Although bacteria have been hypothesized as agents of carcinogenesis, little is known about the microbiota profile of NSCLC and common histological subtypes: adenocarcinoma (ADC) and squamous cell carcinoma (SCC); or the impact of COPD comorbidity in its composition. To fill this gap, we performed a wide characterization of lung microbiota using a pooled sequencing approach of 16S ribosomal RNA gene, covering a total of 103 bronchoalveaolar lavage samples. Next, identified taxa were used to guide the surveying of 509 ADC and 500 SCC tumor samples from The Cancer Genome Atlas and the annotation of unmapped RNAseq reads. In the analysis of microbial data several clinical variables were considered along with cancer subtype, namely history of cigarette smoking and airflow obstruction, affected lung region and gender. Globally, we showed that NSCLC microbiota is enriched in Proteobacteria and more diverse in SCC than ADC, particularly in males and heavier smokers. Tumor localization and cancer stage had no effect in microbiota diversity. High frequencies of Proteobacteria were found to discriminate a major cluster of NSCLC cases, which could be further subdivided into two well-defined bacterial communities associated with either ADC or SCC (Fig.1).\n\nHere, the SCC group was found to diverge from other cases by a worse patient survival and to be defined by Enterobacteriaceae and Achromobacter, correlated also with COPD. This study provides evidence for a link between lung microbiota and NSCLC subtypes and for its influence on patient life expectancy.