The airway microbiota of non‐small cell lung cancer patients and its relationship to tumor stage andEGFRgene mutation

Abstract

Background: Accumulating studies have suggested the airway microbiota in lung cancer patients is significantly different from that of healthy controls. However, little is known about the relationship between airway microbiota and important clinical parameters of lung cancer. In this study, we aimed to explore the association between sputum microbiota and lung cancer stage, lymph node metastasis, intrathoracic metastasis, and epidermal growth factor receptor (EGFR) gene mutation. Methods: The microbiota of sputum samples from 85 newly-diagnosed NSCLC patients were sequenced via 16S rRNA sequencing of the V3-V4 region. Sequencing reads were filtered using QIIME2 and clustered against UPARSE. Results: Alpha-and β-diversity was significantly different between patients in stages I to II (early stage, ES) and patients in stages III to IV (advanced stage, AS). Linear discriminant analysis Effect Size (LEfSe) identified that genera Granulicatella and Actinobacillus were significantly enriched in ES, and the genus Actinomyces was significantly enriched in AS. PICRUSt2 identified that the NAD salvage pathway was significantly enriched in AS, which was positively associated with Granulicatella. Patients with intrathoracic metastasis were associated with increased genus Peptostreptococcus and incomplete reductive TCA cycle, which was associated with increased Peptostreptococcus. Genera Parvimonas, Pseudomona and L-valine biosynthesis were positively associated with lymph node metastasis. L-valine biosynthesis was related with increased Pseudomona. Finally, the genus Parvimonas was significantly enriched in adenocarcinoma patients with EGFR mutation. Conclusion:The taxonomy structure differed between different lung cancer stages. The tumor stage, intrathoracic metastasis, lymph node metastasis, and EGFR mutation were associated with alteration of specific airway genera and metabolic function of sputum microbiota.

Exploring Co-occurrence patterns and microbial diversity in the lung microbiome of patients with non-small cell lung cancer

“…Additionally, we did not find a marked difference between the two groups in the taxonomic composition (beta diversity). Different studies reported different alpha and beta diversity results in lung cancer, including increased alpha diversity [ 15 , 16 ], decreased alpha diversity [ 17 , 18 ], increased beta diversity [ 19 , 20 ], decreased beta diversity [ 17 , 21 , 22 ], and no diversity changes [ 21 , 23 ]. Overall, these results indicate that there is still no definite consensus about the diversity of the lung microbiome composition in lung cancer.…”

The microbiome in the pathogenesis of lung cancer

“…During the early stage (stage I–II) of NSCLC, Firmicutes, Bacillus , and Actinobacteria were significantly enriched. Actinobacteria were remarkably enriched during the late stage (stage III–IV) [14]. Additionally, the species of bacteria that are observed in lung cancer depend on the sampling site and the classification of pathology.…”

“…Epidermal growth factor receptor (EGFR) mutation is a major prognostic factor in LUAD patients. Numerous studies have shown that EGFR mutation is positively correlated with the abundance of Bacteroides , Parvimonas , and Actinobacillus [14]. One recent study indicated that treponema and fibrillar factor could be used as biomarkers of lung cancer in tests of saliva and BALF samples [44].…”

“…Similarly, emerging pathogens have been found that cause high-risk lung cancer, such as high-risk human papillomaviruses (HR-HPVs), cytomegalovirus, influenza virus, and measles virus (MV) [9][10][11][12]. In addition, accumulating studies have revealed the correlation of specific microbiota with lung cancer, such as Firmicutes, Proteobacteria, Actinobacteria, and Veillonella [13][14][15]. Several studies have proposed that the microbiome might serve as a potential marker and therapeutic target of lung cancer through high-throughput sequencing [16].…”

Pragmatic Expectancy on Microbiota and Non-Small Cell Lung Cancer: A Narrative Review

“…The main attention has been devoted to the correlation of EGFR status and lung microbiome, and experimental reports already suggested that in bronchoscopy-obtained NSCLC samples, the detection of EGFR-mutant cells has been correlated with the abundance of rare species, such as Rhizopus oryzae, Natronolimnobius innermongolicus, Staphylococcus sciuri [18]. The genus Parvimonas has been documented to be significantly enriched in EGFR-mutant adenocarcinomas as well [53]. Similarly, in colorectal cancer, the occurrence of somatic mutations affecting the KRAS oncogene has been significantly associated with the composition of intestinal flora, namely Roseburia, Parabacteroides, Metascardovia, Staphylococcus and Bacillales, thus promoting cancer onset [54].…”