Interaction between the microbiome and TP53 in human lung cancer

Abstract

BackgroundLung cancer is the leading cancer diagnosis worldwide and the number one cause of cancer deaths. Exposure to cigarette smoke, the primary risk factor in lung cancer, reduces epithelial barrier integrity and increases susceptibility to infections. Herein, we hypothesize that somatic mutations together with cigarette smoke generate a dysbiotic microbiota that is associated with lung carcinogenesis. Using lung tissue from 33 controls and 143 cancer cases, we conduct 16S ribosomal RNA (rRNA) bacterial gene sequencing, with RNA-sequencing data from lung cancer cases in The Cancer Genome Atlas serving as the validation cohort.ResultsOverall, we demonstrate a lower alpha diversity in normal lung as compared to non-tumor adjacent or tumor tissue. In squamous cell carcinoma specifically, a separate group of taxa are identified, in which Acidovorax is enriched in smokers. Acidovorax temporans is identified within tumor sections by fluorescent in situ hybridization and confirmed by two separate 16S rRNA strategies. Further, these taxa, including Acidovorax, exhibit higher abundance among the subset of squamous cell carcinoma cases with TP53 mutations, an association not seen in adenocarcinomas.ConclusionsThe results of this comprehensive study show both microbiome-gene and microbiome-exposure interactions in squamous cell carcinoma lung cancer tissue. Specifically, tumors harboring TP53 mutations, which can impair epithelial function, have a unique bacterial consortium that is higher in relative abundance in smoking-associated tumors of this type. Given the significant need for clinical diagnostic tools in lung cancer, this study may provide novel biomarkers for early detection.Electronic supplementary materialThe online version of this article (10.1186/s13059-018-1501-6) contains supplementary material, which is available to authorized users.

Network Pharmacology Revealed the mechanism of Platycodon grandiflorum in Lung Cancer Treatment

“…It was speculated that EGFR might been one of the key targets of Platycodon grandi orum. The mutation of TP53 might damage the function of lung epithelium, changed the pulmonary microbial community, and allowed tumor foraging bacteria to proliferate [54] . TP53 stimulated apoptosis of NSCLC cells and lung cancer stem cells [55] .…”

Microbiota Core in Central Lung Cancer with Streptococcal Enrichment as a Possible Diagnostic Marker

“…However, recent data clearly indicate that the microbiota contributes to the prognosis of cancer and determines the response to treatments, particularly responses to the new immunomodulatory therapies [9,28]. Criteria for the normal composition of lung microbiota have not yet been established, but the available data indicate that their composition in cancer patients differs considerably from that of healthy individuals [4][5][6][7][8].…”

“…Significant differences in the lung ecosystem have been described based on health status or a lung cancer diagnosis in sputum [33], bronchoalveolar lavage [5], protected specimen brushing [6], cytological brushing [34], and surgical tissue [7,8,35]. The major contribution of our work is the study of the microbiome surrounding central cancer via direct sampling, but our results are not necessarily applicable to the distal airway.…”

“…Dysbiosis is typically detected surrounding tumors tissues [3], and this trait has been poorly explored in the respiratory airway tissues, and using only surgical samples [4][5][6][7][8]. An understanding of the microbiota is necessary to decipher its possible causal role in cancer, and also to elucidate the prognosis and response to immunomodulatory therapies, because microorganisms and/or their metabolites shape the local microenvironment, influence the immune response, and impact the final battle against cancer [9].…”

Author Correction: Interaction between the microbiome and TP53 in human lung cancer

“…Following publication of the original paper [1], the authors submitted a new Additional file 5 to replace the one containing formatting issues. The updated Additional file 5 is published in this correction.…”