Metabolic/hypoxial axis predicts tamoxifen resistance in breast cancer
Abstract We sought in our cross-sectional study to investigate the role of metabolic/hypoxial axis in the development of tamoxifen (TMX) resistance in BC patients. Quantification of plasma LncRNA Taurine upregulated-1 (TUG-1), miRNA 186-5p (miR-186), serum Sirtuin-3 (SIRT3), Peroxisome Proliferator...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-19977-w |
| _version_ | 1811253736471789568 |
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| author | Hany N. Azzam Marwa O. El-Derany Sara A. Wahdan Reham M. Faheim Gouda K. Helal Ebtehal El-Demerdash |
| author_facet | Hany N. Azzam Marwa O. El-Derany Sara A. Wahdan Reham M. Faheim Gouda K. Helal Ebtehal El-Demerdash |
| author_sort | Hany N. Azzam |
| collection | DOAJ |
| description | Abstract We sought in our cross-sectional study to investigate the role of metabolic/hypoxial axis in the development of tamoxifen (TMX) resistance in BC patients. Quantification of plasma LncRNA Taurine upregulated-1 (TUG-1), miRNA 186-5p (miR-186), serum Sirtuin-3 (SIRT3), Peroxisome Proliferator Activator Receptor alpha (PPAR-1 α) and Hypoxia Inducible Factor-1 (HIF-1α) was done in a cohort of patients divided into TMX-sensitive and TMX-resistant candidates. Multiple logistic regression and Receiver Operating Characteristic curve were developed for significant predictors. Plasma TUG-1 and miR-186 were significantly elevated in TMX resistant patients. Serum proteins SIRT3, PPAR-1 α and HIF-1α were deficient in TMX resistant patients compared to TMX sensitive patients, respectively. miR-186 was associated with respiratory symptoms, while, HIF-1α was associated with metastases in TMX resistant patients. Strong correlations were found between all parameters. A predictive model was constructed with TUG-1 and HIF-1α to estimate TMX resistance in BC patients with 88.3% sensitivity and 91.6% specificity. Hypoxia and metabolic dysregulations play important role in the development of TMX resistance in BC patients. Correlation between hypoxia, carcinogenesis and patient’s mortality have led to more aggressive phenotypes, increased risk of metastasis and resistance to TMX. |
| first_indexed | 2024-04-12T16:55:35Z |
| format | Article |
| id | doaj.art-50bf80bedb1f42b3bbb85e9fc2b1511e |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-12T16:55:35Z |
| publishDate | 2022-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-50bf80bedb1f42b3bbb85e9fc2b1511e2022-12-22T03:24:15ZengNature PortfolioScientific Reports2045-23222022-09-0112111310.1038/s41598-022-19977-wMetabolic/hypoxial axis predicts tamoxifen resistance in breast cancerHany N. Azzam0Marwa O. El-Derany1Sara A. Wahdan2Reham M. Faheim3Gouda K. Helal4Ebtehal El-Demerdash5Department of Pharmacology and Toxicology, Faculty of Pharmacy, Heliopolis UniversityDepartment of Biochemistry, Faculty of Pharmacy, Ain Shams UniversityDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams UniversityDepartment of Clinical Oncology and Nuclear Medicine, Faculty of Medicine, Ain Shams UniversityDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Heliopolis UniversityDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams UniversityAbstract We sought in our cross-sectional study to investigate the role of metabolic/hypoxial axis in the development of tamoxifen (TMX) resistance in BC patients. Quantification of plasma LncRNA Taurine upregulated-1 (TUG-1), miRNA 186-5p (miR-186), serum Sirtuin-3 (SIRT3), Peroxisome Proliferator Activator Receptor alpha (PPAR-1 α) and Hypoxia Inducible Factor-1 (HIF-1α) was done in a cohort of patients divided into TMX-sensitive and TMX-resistant candidates. Multiple logistic regression and Receiver Operating Characteristic curve were developed for significant predictors. Plasma TUG-1 and miR-186 were significantly elevated in TMX resistant patients. Serum proteins SIRT3, PPAR-1 α and HIF-1α were deficient in TMX resistant patients compared to TMX sensitive patients, respectively. miR-186 was associated with respiratory symptoms, while, HIF-1α was associated with metastases in TMX resistant patients. Strong correlations were found between all parameters. A predictive model was constructed with TUG-1 and HIF-1α to estimate TMX resistance in BC patients with 88.3% sensitivity and 91.6% specificity. Hypoxia and metabolic dysregulations play important role in the development of TMX resistance in BC patients. Correlation between hypoxia, carcinogenesis and patient’s mortality have led to more aggressive phenotypes, increased risk of metastasis and resistance to TMX.https://doi.org/10.1038/s41598-022-19977-w |
| spellingShingle | Hany N. Azzam Marwa O. El-Derany Sara A. Wahdan Reham M. Faheim Gouda K. Helal Ebtehal El-Demerdash Metabolic/hypoxial axis predicts tamoxifen resistance in breast cancer Scientific Reports |
| title | Metabolic/hypoxial axis predicts tamoxifen resistance in breast cancer |
| title_full | Metabolic/hypoxial axis predicts tamoxifen resistance in breast cancer |
| title_fullStr | Metabolic/hypoxial axis predicts tamoxifen resistance in breast cancer |
| title_full_unstemmed | Metabolic/hypoxial axis predicts tamoxifen resistance in breast cancer |
| title_short | Metabolic/hypoxial axis predicts tamoxifen resistance in breast cancer |
| title_sort | metabolic hypoxial axis predicts tamoxifen resistance in breast cancer |
| url | https://doi.org/10.1038/s41598-022-19977-w |
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