Identifying Hub Genes Associated with Neoadjuvant Chemotherapy Resistance in Breast Cancer and Potential Drug Repurposing for the Development of Precision Medicine
Breast cancer is the second leading cause of morbidity and mortality in women worldwide. Despite advancements in the clinical application of neoadjuvant chemotherapy (NAC), drug resistance remains a major concern hindering treatment efficacy. Thus, identifying the key genes involved in driving NAC r...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/20/12628 |
| _version_ | 1797472714311598080 |
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| author | Trishna Saha Detroja Rajesh Detroja Sumit Mukherjee Abraham O. Samson |
| author_facet | Trishna Saha Detroja Rajesh Detroja Sumit Mukherjee Abraham O. Samson |
| author_sort | Trishna Saha Detroja |
| collection | DOAJ |
| description | Breast cancer is the second leading cause of morbidity and mortality in women worldwide. Despite advancements in the clinical application of neoadjuvant chemotherapy (NAC), drug resistance remains a major concern hindering treatment efficacy. Thus, identifying the key genes involved in driving NAC resistance and targeting them with known potential FDA-approved drugs could be applied to advance the precision medicine strategy. With this aim, we performed an integrative bioinformatics study to identify the key genes associated with NAC resistance in breast cancer and then performed the drug repurposing to identify the potential drugs which could use in combination with NAC to overcome drug resistance. In this study, we used publicly available RNA-seq datasets from the samples of breast cancer patients sensitive and resistant to chemotherapy and identified a total of 1446 differentially expressed genes in NAC-resistant breast cancer patients. Next, we performed gene co-expression network analysis to identify significantly co-expressed gene modules, followed by MCC (Multiple Correlation Clustering) clustering algorithms and identified 33 key hub genes associated with NAC resistance. mRNA–miRNA network analysis highlighted the potential impact of these hub genes in altering the regulatory network in NAC-resistance breast cancer cells. Further, several hub genes were found to be significantly involved in the poor overall survival of breast cancer patients. Finally, we identified FDA-approved drugs which could be useful for potential drug repurposing against those hub genes. Altogether, our findings provide new insight into the molecular mechanisms of NAC resistance and pave the way for drug repurposing techniques and personalized treatment to overcome NAC resistance in breast cancer. |
| first_indexed | 2024-03-09T20:05:08Z |
| format | Article |
| id | doaj.art-baaf7db6acaf4987bcec563e2460d501 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T20:05:08Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-baaf7db6acaf4987bcec563e2460d5012023-11-24T00:34:34ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123201262810.3390/ijms232012628Identifying Hub Genes Associated with Neoadjuvant Chemotherapy Resistance in Breast Cancer and Potential Drug Repurposing for the Development of Precision MedicineTrishna Saha Detroja0Rajesh Detroja1Sumit Mukherjee2Abraham O. Samson3The Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, IsraelThe Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, IsraelDepartment of Computer Science, Ben-Gurion University, Beer-Sheva 8410501, IsraelThe Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, IsraelBreast cancer is the second leading cause of morbidity and mortality in women worldwide. Despite advancements in the clinical application of neoadjuvant chemotherapy (NAC), drug resistance remains a major concern hindering treatment efficacy. Thus, identifying the key genes involved in driving NAC resistance and targeting them with known potential FDA-approved drugs could be applied to advance the precision medicine strategy. With this aim, we performed an integrative bioinformatics study to identify the key genes associated with NAC resistance in breast cancer and then performed the drug repurposing to identify the potential drugs which could use in combination with NAC to overcome drug resistance. In this study, we used publicly available RNA-seq datasets from the samples of breast cancer patients sensitive and resistant to chemotherapy and identified a total of 1446 differentially expressed genes in NAC-resistant breast cancer patients. Next, we performed gene co-expression network analysis to identify significantly co-expressed gene modules, followed by MCC (Multiple Correlation Clustering) clustering algorithms and identified 33 key hub genes associated with NAC resistance. mRNA–miRNA network analysis highlighted the potential impact of these hub genes in altering the regulatory network in NAC-resistance breast cancer cells. Further, several hub genes were found to be significantly involved in the poor overall survival of breast cancer patients. Finally, we identified FDA-approved drugs which could be useful for potential drug repurposing against those hub genes. Altogether, our findings provide new insight into the molecular mechanisms of NAC resistance and pave the way for drug repurposing techniques and personalized treatment to overcome NAC resistance in breast cancer.https://www.mdpi.com/1422-0067/23/20/12628breast cancerneoadjuvant chemotherapy (NAC) resistanceco-expressiondrug repurposingprecision medicine |
| spellingShingle | Trishna Saha Detroja Rajesh Detroja Sumit Mukherjee Abraham O. Samson Identifying Hub Genes Associated with Neoadjuvant Chemotherapy Resistance in Breast Cancer and Potential Drug Repurposing for the Development of Precision Medicine International Journal of Molecular Sciences breast cancer neoadjuvant chemotherapy (NAC) resistance co-expression drug repurposing precision medicine |
| title | Identifying Hub Genes Associated with Neoadjuvant Chemotherapy Resistance in Breast Cancer and Potential Drug Repurposing for the Development of Precision Medicine |
| title_full | Identifying Hub Genes Associated with Neoadjuvant Chemotherapy Resistance in Breast Cancer and Potential Drug Repurposing for the Development of Precision Medicine |
| title_fullStr | Identifying Hub Genes Associated with Neoadjuvant Chemotherapy Resistance in Breast Cancer and Potential Drug Repurposing for the Development of Precision Medicine |
| title_full_unstemmed | Identifying Hub Genes Associated with Neoadjuvant Chemotherapy Resistance in Breast Cancer and Potential Drug Repurposing for the Development of Precision Medicine |
| title_short | Identifying Hub Genes Associated with Neoadjuvant Chemotherapy Resistance in Breast Cancer and Potential Drug Repurposing for the Development of Precision Medicine |
| title_sort | identifying hub genes associated with neoadjuvant chemotherapy resistance in breast cancer and potential drug repurposing for the development of precision medicine |
| topic | breast cancer neoadjuvant chemotherapy (NAC) resistance co-expression drug repurposing precision medicine |
| url | https://www.mdpi.com/1422-0067/23/20/12628 |
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