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hao Zeng
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FP07 - Pathology (ID 109)
- Event: WCLC 2020
- Type: Posters (Featured)
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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FP07.01 - Dysbiosis of Gut Microbiota Suppress the Brain Metastasis of Non-Small Cell Lung Cancer (ID 1501)
00:00 - 00:00 | Author(s): hao Zeng
- Abstract
Introduction
Brain metastasis (BM) is associated with poor prognosis in patients with advanced non-small cell lung cancer (NSCLC), gut microbiota have been reported involved in the development of NSCLC. However, the impact of the gut microbiota on BM of NSCLC is still vague to date. This study aimed to explore the potential mechanism of gut microbiota dysbiosis on BM of NSCLC.
Methods
We collected 85 fecal samples from NSCLC patients with or without BM, and performed 16S rRNA gene sequencing. Conventional C57BL/6 mice were treated with an antibiotic cocktail to deplete the gut microbiota. The effects of gut microbiota dysbiosis was investigated in vivo by using NSCLC BM mouse models.
Results
There are no obvious difference in the microbial diversity and composition between NSCLC patients with BM (BM+, n=25) and without BM group (BM-, n=60). However, several differentially abundant genera were identified between subject groups by LEfSe analysis and Wilcoxon rank-sum test. Blautia, the genus implicated in central nervous system disorder, significantly decreased in BM+ group comparing to BM- group. Furthermore, the tumor burden significantly reduced in antibiotics-treated BM mice model, along with increased microglia cells by flow cytometry analysis. Remarkably, fecal bacteria transplantation (FMT) reduced gut microbial dysbiosis, partially attenuate the antibiotic-mediated tumor inhibition.
Conclusion
These results indicate that gut microbiota dysbiosis modulate BM of NSCLC, and Blautia, was putative microbial biomarkers that exclusively associated with BM. Mice experiments suggest that gut microbial dysbiosis inhibit BM by increasing the number of microglia. FMT suggest that BM inhibition mediated by gut microbial disorder is weakened by restoring normal microbiota, and warrant further research on the function of microglia.
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P63 - Tumor Biology and Systems Biology - Basic and Translational Science - Metastases (ID 201)
- Event: WCLC 2020
- Type: Posters
- Track: Tumor Biology and Systems Biology - Basic and Translational Science
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P63.04 - Dysbiosis of Sputum and Gut Microbiota Modulate Development and Distant Metastasis of Non-Small Cell Lung Carcinomas (ID 1584)
00:00 - 00:00 | Author(s): hao Zeng
- Abstract
Introduction
Lung cancer (LC) is the leading cause of cancer-related deaths mortality worldwide, with non-small cell lung cancer (NSCLC) being the most common form of LC. Despite the recent development of therapies for NSCLC, tumor metastasis is the main cause of recurrence and mortality in patients with NSCLC. Although dysbiosis of lung and gut microbiota have been associated with NSCLC, their relative contributions are unclear. In addition, their roles in distant metastasis (DM) are still illusive.
Methods
We enrolled in total 121 individuals who completed our study protocol. Among which, 87 were newly diagnosed with NSCLC who had not previously received any anticancer therapy nor treated with any antibiotics, while 34 were healthy volunteers. We classified patients into distinct disease stages (i.e. from I to IV) according to the 8th American Joint Committee on Cancer guidelines. Then, we collected in total 30 sputum and 29 fecal samples from the healthy controls and 66 sputum and 85 fecal samples from the NSCLC patients, and submitted them for 16S sequencing. To further validate microbiota play important roles in the development of NSCLC, we treated C57BL/6 adult female mice (six weeks of age) with antibiotic cocktail (ABX) of vancomycin, neomycin, ampicillin and metronidazol in drinking water starting 2 weeks before tumor inoculation. Subcutaneous tumor model was established by injecting murine Lewis lung cancer cell tagged with luciferences (LLC-luc) in the subcutaneous layer of C57BL/6 mice's right back.
Results
We found significant perturbations of gut- and sputum- microbiota in patients with NSCLC and DM. We obtained better Machine-learning models for patient stratification using both microbiota than either dataset, with the highest area under the curve (AUC) value of 0.842; surprisingly, sputum- microbiota contributed more than the gut. Several microbial-biomarkers were shared by both microbiota, indicating their similar roles at distinct body sites. Microbial-biomarkers of distinct disease stages were mostly shared, suggesting biomarkers for distant metastasis could be acquired early. Surprisingly, Pseudomonas aeruginosa, a species previously associated with wound infections, was associated with brain metastasis, indicating distinct types of DMs could have different microbial-biomarkers. Furthermore, we found significantly larger tumors in antibiotics-treated mice, confirming that microbiota dysbiosis could indeed promote tumor growth.
Conclusion
Our results indicate that in addition to gut-microbiota, sputum-microbiota could contribute significantly to NSCLC and distant metastasis, and improve the performance of patient-stratification models. Mice experiments suggest that favorable clinical outcomes could be accomplished by restoring normal microbiota, and warrant further research on the underlying molecular mechanisms.
