Live or Heat-Killed Lactobacillus rhamnosus Aerosolization Decreases Adenomatous Lung Cancer Development in a Mouse Carcinogen-Induced Tumor Model
Abstract
:1. Introduction
2. Results
2.1. Effect of Aerosolized Vancomycin/Neomycin and Lactobacillus rhamnosus GG on Primary Adenomatous Lung Cancer Development
2.2. Transcriptional Profiling of Aerosolized Vanco/Neo and L.RGG Adenomatous Cancer Bearing Lungs
2.3. L. rhamnosus GG-Up-Modulated J Chain Gene Is Associated with Survival of Lung Adenocarcinoma Patients
3. Discussion
4. Materials and Methods
4.1. Mice and Experimental Protocols
4.2. Metagenomic Analysis of Bronchoalveolar Lavage
4.3. Gene Expression Profiling and Immune Infiltrating Populations Analyses
4.4. Immunohistochemistry Analysis
4.5. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Gene Symbol | Description | Heat killed L.RGG Aer, Avg (SD), log2 | Saline, Avg (SD), log2 | Fold Change | P-val | FDR P-val |
---|---|---|---|---|---|---|
Dnajc11 | DnaJ (Hsp40) homolog, subfamily C, member 11 | 8.59 (0.74) | 9.97 (0.29) | −2.60 | 1.01 × 106 | 0.0112 |
Jchain | immunoglobulin joining chain | 10.69 (1.61) | 7.66 (0.82) | 8.21 | 8.15 × 106 | 0.0303 |
Vmn1r73 | vomeronasal 1 receptor 73 | 6.31 (0.72) | 5.19 (0.23) | 2.18 | 3.11 × 105 | 0.0406 |
Six1 | sine oculis-related homeobox 1 | 11.89 (0.89) | 10.26 (0.95) | 3.10 | 3.48 × 105 | 0.0419 |
Gm3468 | predicted gene 3468 | 9.66 (1.08) | 8.50 (0.35) | 2.24 | 4.86 × 105 | 0.0461 |
Atp6v0d2 | ATPase, H+ transporting, lysosomal V0 subunit D2 | 8.69 (0.52) | 10.11 (0.69) | −2.67 | 5.21 × 105 | 0.0461 |
Scimp | SLP adaptor and CSK interacting membrane protein | 7.34 (0.45) | 8.42 (0.60) | −2.11 | 7.84 × 105 | 0.0461 |
Gm16506 | predicted gene 16506 | 7.65 (0.72) | 6.63 (0.26) | 2.03 | 9.12 × 105 | 0.0461 |
Zdhhc21 | zinc finger, DHHC domain containing 21 | 8.24 (0.88) | 9.32 (0.35) | −2.11 | 2.00 × 104 | 0.0485 |
Rhox8 | reproductive homeobox 8 | 6.33 (0.82) | 5.32 (0.33) | 2.01 | 2.00 × 104 | 0.0485 |
Git1 | G protein-coupled receptor kinase-interactor 1 | 7.29 (0.64) | 8.41 (0.42) | −2.19 | 2.00 × 104 | 0.0485 |
Gene Symbol | Description | Live L.RGG Aer, Avg (SD), log2 | Saline, Avg (SD), log2 | Fold Change | P-val | FDR P-val |
---|---|---|---|---|---|---|
Jchain | immunoglobulin joining chain | 11.87 (1.17) | 7.66 (0.82) | 18.49 | 2.20 × 108 | 0.0005 |
Multivariate Analysis in Lung Cancer Patients (OS) | ||
---|---|---|
p Value | Hazard Ratio | |
Stage | 0 | 1.66 (1.35–2.03) |
Smoking history | 0.055 | 0.65 (0.41–1.01) |
Jchain gene | 0 | 0.51 (0.38–0.7) |
Multivariate Analysis in Lung Adenocarcinoma Patients (OS) | ||
---|---|---|
p Value | Hazard Ratio | |
Stage | 0 | 2.42 (1.77–3.31) |
Smoking history | 0.0308 | 0.59 (0.37–0.95) |
Jchain gene | 0.0011 | 0.5 (0.33–0.76) |
Multivariate Analysis in Lung Cancer Patients (FP) | ||
---|---|---|
p Value | Hazard Ratio | |
Stage | 0 | 2.12 (1.63–2.76) |
Smoking history | 0.8614 | 1.03 (0.71–1.51) |
Jchain gene | 0.0008 | 0.56 (0.4–0.79) |
Multivariate Analysis in Lung Adenocarcinoma Patients (FP) | ||
---|---|---|
p Value | Hazard Ratio | |
Stage | 0 | 2.16 (1.61–2.89) |
Smoking history | 0.7501 | 0.94 (0.64–1.39) |
Jchain gene | 0.0017 | 0.55 (0.38–0.8) |
Primary Antibody | Clone | Supplier and Code | Clonality | Working Dilution | Secondary Antibody | Supplier and Code | Working Dilution |
---|---|---|---|---|---|---|---|
FoxP3 | FJK-16S | eBioscience (14-5773-82) | Rat monoclonal | 1:200 | Anti-rat IgG | Vector (VC-BA-4001-MC05) | 1:200 |
IgA alpha chain | \ | Prodotti Gianni Srl (ab97233) | Goat polyclonal | 1:1500 | Anti-goat IgG | Vector (VC-BA-5000-MM15) | 1:200 |
J chain | SP105 | Invitrogen (MA5-16419) | Rabbit monoclonal | 1:500 | Anti-rabbit IgG | Vector (VC-BA-1000-MM15) | 1:200 |
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Le Noci, V.; Bernardo, G.; Manenti, G.; Infante, G.; Khaleghi Hashemian, D.; Minoli, L.; Canesi, S.; Bianchi, F.; Triulzi, T.; Arioli, S.; et al. Live or Heat-Killed Lactobacillus rhamnosus Aerosolization Decreases Adenomatous Lung Cancer Development in a Mouse Carcinogen-Induced Tumor Model. Int. J. Mol. Sci. 2022, 23, 12748. https://doi.org/10.3390/ijms232112748
Le Noci V, Bernardo G, Manenti G, Infante G, Khaleghi Hashemian D, Minoli L, Canesi S, Bianchi F, Triulzi T, Arioli S, et al. Live or Heat-Killed Lactobacillus rhamnosus Aerosolization Decreases Adenomatous Lung Cancer Development in a Mouse Carcinogen-Induced Tumor Model. International Journal of Molecular Sciences. 2022; 23(21):12748. https://doi.org/10.3390/ijms232112748
Chicago/Turabian StyleLe Noci, Valentino, Giancarla Bernardo, Giacomo Manenti, Gabriele Infante, Dariush Khaleghi Hashemian, Lucia Minoli, Simone Canesi, Francesca Bianchi, Tiziana Triulzi, Stefania Arioli, and et al. 2022. "Live or Heat-Killed Lactobacillus rhamnosus Aerosolization Decreases Adenomatous Lung Cancer Development in a Mouse Carcinogen-Induced Tumor Model" International Journal of Molecular Sciences 23, no. 21: 12748. https://doi.org/10.3390/ijms232112748