Abstract

Background: Association between oral bacteria and increased risk of lung cancer have been reported in several previous studies, however, the potential association between salivary microbiome and lung cancer in non-smoking women have not been evaluated. There is also no report on the relationship between immunocytochemistry markers and salivary microbiota.Method: In this study, we assessed the salivary microbiome of 75 non-smoking female lung cancer patients and 172 matched healthy individuals using 16S rRNA gene amplicon sequencing. We also calculated the Spearman's rank correlation coefficient between salivary microbiota and three immunohistochemical markers (TTF-1, Napsin A and CK7).Result: We analyzed the salivary microbiota of 247 subjects and found that non-smoking female lung cancer patients exhibited oral microbial dysbiosis. There was significantly lower microbial diversity and richness in lung cancer patients when compared to the control group (Shannon index, P < 0.01; Ace index, P < 0.0001). Based on the analysis of similarities, the composition of the microbiota in lung cancer patients also differed from that of the control group (r = 0.454, P < 0.001, unweighted UniFrac; r = 0.113, P < 0.01, weighted UniFrac). The bacterial genera Sphingomonas (P < 0.05) and Blastomonas (P < 0.0001) were relatively higher in non-smoking female lung cancer patients, whereas Acinetobacter (P < 0.001) and Streptococcus (P < 0.01) were higher in controls. Based on Spearman's correlation analysis, a significantly positive correlation can be observed between CK7 and Enterobacteriaceae (r = 0.223, P < 0.05). At the same time, Napsin A was positively associated with genera Blastomonas (r = 0.251, P < 0.05). TTF-1 exhibited a significantly positive correlation with Enterobacteriaceae (r = 0.262, P < 0.05). Functional analysis from inferred metagenomes indicated that oral microbiome in non-smoking female lung cancer patients were related to cancer pathways, p53 signaling pathway, apoptosis and tuberculosis.Conclusions: The study identified distinct salivary microbiome profiles in non-smoking female lung cancer patients, revealed potential correlations between salivary microbiome and immunocytochemistry markers used in clinical diagnostics, and provided proof that salivary microbiota can be an informative source for discovering non-invasive lung cancer biomarkers.

Highlights

  • Lung cancer is considered the leading cause of cancer death worldwide, accounting for over 300,000 deaths annually [1]

  • We identified the relationship between salivary microbiota and immunocytochemistry markers containing thyroid transcription factor(TTF-1), Napsin A and cytokeratin(CK7), as well as the specific microbial signatures of lung cancer [24, 25]

  • 247 participants including 75 non-smoking female lung cancer patients and 172 healthy controls were recruited for this study

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Summary

Introduction

Lung cancer is considered the leading cause of cancer death worldwide, accounting for over 300,000 deaths annually [1]. Non-smoking lung cancer patients are often considered a different population [4]. Cigarette smoking may lead to oral microbiome imbalance, thereby causing potential shifts in functional pathways, and having implications for smoking-related diseases [21]. Previous studies on oral microbiome in lung cancer have not stratified clinical samples based on the smoking status and fully evaluated confounding factors such as smoking on the discovered bacterial biomarkers [18]. There has been no report on characterizing oral microbiome in non-smoking female lung cancer patients. Association between oral bacteria and increased risk of lung cancer have been reported in several previous studies, the potential association between salivary microbiome and lung cancer in non-smoking women have not been evaluated. There is no report on the relationship between immunocytochemistry markers and salivary microbiota

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