Exosomal miRNAs as Novel Pharmacodynamic Biomarkers for Cancer Chemopreventive Agent Early Stage Treatments in Chemically Induced Mouse Model of Lung Squamous Cell Carcinoma
Background: Chemopreventive agent (CPA) treatment is one of the main preventive options for lung cancer. However, few studies have been done on pharmacodynamic biomarkers of known CPAs for lung cancer. Materials and methods: In this study, we treated mouse models of lung squamous cell carcinoma with...
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MDPI AG
2019-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/11/4/477 |
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| author | Yu Zhou Qi Zhang Meijun Du Donghai Xiong Yian Wang Altaf Mohammed Ronald A. Lubet Liang Wang Ming You |
| author_facet | Yu Zhou Qi Zhang Meijun Du Donghai Xiong Yian Wang Altaf Mohammed Ronald A. Lubet Liang Wang Ming You |
| author_sort | Yu Zhou |
| collection | DOAJ |
| description | Background: Chemopreventive agent (CPA) treatment is one of the main preventive options for lung cancer. However, few studies have been done on pharmacodynamic biomarkers of known CPAs for lung cancer. Materials and methods: In this study, we treated mouse models of lung squamous cell carcinoma with three different CPAs (MEK inhibitor: AZD6244, PI-3K inhibitor: XL-147 and glucocorticoid: Budesonide) and examined circulating exosomal miRNAs in the plasma of each mouse before and after treatment. Results: Compared to baselines, we found differentially expressed exosomal miRNAs after AZD6244 treatment (<i>n</i> = 8, FDR < 0.05; <i>n</i> = 55, raw <i>p</i>-values < 0.05), after XL-147 treatment (<i>n</i> = 4, FDR < 0.05; <i>n</i> = 26, raw <i>p</i>-values < 0.05) and after Budesonide treatment (<i>n</i> = 1, FDR < 0.05; <i>n</i> = 36, raw <i>p</i>-values < 0.05). In co-expression analysis, we found that modules of exosomal miRNAs reacted to CPA treatments differently. By variable selection, we identified 11, 9 and nine exosomal miRNAs as predictors for AZD6244, XL-147 and Budesonide treatment, respectively. Integrating all the results, we highlighted 4 miRNAs (mmu-miR-215-5p, mmu-miR-204-5p, mmu-miR-708-3p and mmu-miR-1298-5p) as the key for AZD6244 treatment, mmu-miR-23a-3p as key for XL-147 treatment, and mmu-miR-125a-5p and mmu-miR-16-5p as key for Budesonide treatment. Conclusions: This is the first study to use circulating exosomal miRNAs as pharmacodynamic biomarkers for CPA treatment in lung cancer. |
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| language | English |
| last_indexed | 2024-03-12T06:04:17Z |
| publishDate | 2019-04-01 |
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| series | Cancers |
| spelling | doaj.art-ebe01d2da4eb49d48a0183815474ef5d2023-09-03T03:47:51ZengMDPI AGCancers2072-66942019-04-0111447710.3390/cancers11040477cancers11040477Exosomal miRNAs as Novel Pharmacodynamic Biomarkers for Cancer Chemopreventive Agent Early Stage Treatments in Chemically Induced Mouse Model of Lung Squamous Cell CarcinomaYu Zhou0Qi Zhang1Meijun Du2Donghai Xiong3Yian Wang4Altaf Mohammed5Ronald A. Lubet6Liang Wang7Ming You8Center for Disease Prevention and Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USACenter for Disease Prevention and Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USADepartment of Pathology, Medical College of Wisconsin, Milwaukee, WI 53226, USACenter for Disease Prevention and Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USACenter for Disease Prevention and Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USAChemopreventive Agent Development Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892, USAChemopreventive Agent Development Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892, USADepartment of Pathology, Medical College of Wisconsin, Milwaukee, WI 53226, USACenter for Disease Prevention and Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USABackground: Chemopreventive agent (CPA) treatment is one of the main preventive options for lung cancer. However, few studies have been done on pharmacodynamic biomarkers of known CPAs for lung cancer. Materials and methods: In this study, we treated mouse models of lung squamous cell carcinoma with three different CPAs (MEK inhibitor: AZD6244, PI-3K inhibitor: XL-147 and glucocorticoid: Budesonide) and examined circulating exosomal miRNAs in the plasma of each mouse before and after treatment. Results: Compared to baselines, we found differentially expressed exosomal miRNAs after AZD6244 treatment (<i>n</i> = 8, FDR < 0.05; <i>n</i> = 55, raw <i>p</i>-values < 0.05), after XL-147 treatment (<i>n</i> = 4, FDR < 0.05; <i>n</i> = 26, raw <i>p</i>-values < 0.05) and after Budesonide treatment (<i>n</i> = 1, FDR < 0.05; <i>n</i> = 36, raw <i>p</i>-values < 0.05). In co-expression analysis, we found that modules of exosomal miRNAs reacted to CPA treatments differently. By variable selection, we identified 11, 9 and nine exosomal miRNAs as predictors for AZD6244, XL-147 and Budesonide treatment, respectively. Integrating all the results, we highlighted 4 miRNAs (mmu-miR-215-5p, mmu-miR-204-5p, mmu-miR-708-3p and mmu-miR-1298-5p) as the key for AZD6244 treatment, mmu-miR-23a-3p as key for XL-147 treatment, and mmu-miR-125a-5p and mmu-miR-16-5p as key for Budesonide treatment. Conclusions: This is the first study to use circulating exosomal miRNAs as pharmacodynamic biomarkers for CPA treatment in lung cancer.https://www.mdpi.com/2072-6694/11/4/477exosomal miRNAspharmacodynamic biomarkerschemopreventive agentlung squamous cell carcinoma |
| spellingShingle | Yu Zhou Qi Zhang Meijun Du Donghai Xiong Yian Wang Altaf Mohammed Ronald A. Lubet Liang Wang Ming You Exosomal miRNAs as Novel Pharmacodynamic Biomarkers for Cancer Chemopreventive Agent Early Stage Treatments in Chemically Induced Mouse Model of Lung Squamous Cell Carcinoma Cancers exosomal miRNAs pharmacodynamic biomarkers chemopreventive agent lung squamous cell carcinoma |
| title | Exosomal miRNAs as Novel Pharmacodynamic Biomarkers for Cancer Chemopreventive Agent Early Stage Treatments in Chemically Induced Mouse Model of Lung Squamous Cell Carcinoma |
| title_full | Exosomal miRNAs as Novel Pharmacodynamic Biomarkers for Cancer Chemopreventive Agent Early Stage Treatments in Chemically Induced Mouse Model of Lung Squamous Cell Carcinoma |
| title_fullStr | Exosomal miRNAs as Novel Pharmacodynamic Biomarkers for Cancer Chemopreventive Agent Early Stage Treatments in Chemically Induced Mouse Model of Lung Squamous Cell Carcinoma |
| title_full_unstemmed | Exosomal miRNAs as Novel Pharmacodynamic Biomarkers for Cancer Chemopreventive Agent Early Stage Treatments in Chemically Induced Mouse Model of Lung Squamous Cell Carcinoma |
| title_short | Exosomal miRNAs as Novel Pharmacodynamic Biomarkers for Cancer Chemopreventive Agent Early Stage Treatments in Chemically Induced Mouse Model of Lung Squamous Cell Carcinoma |
| title_sort | exosomal mirnas as novel pharmacodynamic biomarkers for cancer chemopreventive agent early stage treatments in chemically induced mouse model of lung squamous cell carcinoma |
| topic | exosomal miRNAs pharmacodynamic biomarkers chemopreventive agent lung squamous cell carcinoma |
| url | https://www.mdpi.com/2072-6694/11/4/477 |
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