Bioinformatics-Based Identification of HDAC Inhibitors as Potential Drugs to Target EGFR Wild-Type Non-Small-Cell Lung Cancer
Patients with EGFR-mutant non-small-cell lung cancer (NSCLC) greatly benefit from EGFR-tyrosine kinase inhibitors (EGFR-TKIs) while the prognosis of patients who lack EGFR-sensitive mutations (EGFR wild type, EGFR-WT) remains poor due to a lack of effective therapeutic strategies. There is an urgent...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-03-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.620154/full |
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doaj-26d540bf9ee2403599d033445e780183 |
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| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Yizhe Wang Chunlei Zheng Chunlei Zheng Chunlei Zheng Wenqing Lu Wenqing Lu Wenqing Lu Duo Wang Duo Wang Duo Wang Yang Cheng Yang Chen Kezuo Hou Kezuo Hou Kezuo Hou Jianfei Qi Yunpeng Liu Yunpeng Liu Yunpeng Liu Xiaofang Che Xiaofang Che Xiaofang Che Xuejun Hu |
| spellingShingle |
Yizhe Wang Chunlei Zheng Chunlei Zheng Chunlei Zheng Wenqing Lu Wenqing Lu Wenqing Lu Duo Wang Duo Wang Duo Wang Yang Cheng Yang Chen Kezuo Hou Kezuo Hou Kezuo Hou Jianfei Qi Yunpeng Liu Yunpeng Liu Yunpeng Liu Xiaofang Che Xiaofang Che Xiaofang Che Xuejun Hu Bioinformatics-Based Identification of HDAC Inhibitors as Potential Drugs to Target EGFR Wild-Type Non-Small-Cell Lung Cancer Frontiers in Oncology non-small cell lung cancer histone deacetylase inhibitor WGCNA EGFR wild type metastasis proliferation |
| author_facet |
Yizhe Wang Chunlei Zheng Chunlei Zheng Chunlei Zheng Wenqing Lu Wenqing Lu Wenqing Lu Duo Wang Duo Wang Duo Wang Yang Cheng Yang Chen Kezuo Hou Kezuo Hou Kezuo Hou Jianfei Qi Yunpeng Liu Yunpeng Liu Yunpeng Liu Xiaofang Che Xiaofang Che Xiaofang Che Xuejun Hu |
| author_sort |
Yizhe Wang |
| title |
Bioinformatics-Based Identification of HDAC Inhibitors as Potential Drugs to Target EGFR Wild-Type Non-Small-Cell Lung Cancer |
| title_short |
Bioinformatics-Based Identification of HDAC Inhibitors as Potential Drugs to Target EGFR Wild-Type Non-Small-Cell Lung Cancer |
| title_full |
Bioinformatics-Based Identification of HDAC Inhibitors as Potential Drugs to Target EGFR Wild-Type Non-Small-Cell Lung Cancer |
| title_fullStr |
Bioinformatics-Based Identification of HDAC Inhibitors as Potential Drugs to Target EGFR Wild-Type Non-Small-Cell Lung Cancer |
| title_full_unstemmed |
Bioinformatics-Based Identification of HDAC Inhibitors as Potential Drugs to Target EGFR Wild-Type Non-Small-Cell Lung Cancer |
| title_sort |
bioinformatics-based identification of hdac inhibitors as potential drugs to target egfr wild-type non-small-cell lung cancer |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Oncology |
| issn |
2234-943X |
| publishDate |
2021-03-01 |
| description |
Patients with EGFR-mutant non-small-cell lung cancer (NSCLC) greatly benefit from EGFR-tyrosine kinase inhibitors (EGFR-TKIs) while the prognosis of patients who lack EGFR-sensitive mutations (EGFR wild type, EGFR-WT) remains poor due to a lack of effective therapeutic strategies. There is an urgent need to explore the key genes that affect the prognosis and develop potentially effective drugs in EGFR-WT NSCLC patients. In this study, we clustered functional modules related to the survival traits of EGFR-WT patients using weighted gene co-expression network analysis (WGCNA). We used these data to establish a two-gene prognostic signature based on the expression of CYP11B1 and DNALI1 by combining the least absolute shrinkage and selection operator (LASSO) algorithms and Cox proportional hazards regression analysis. Following the calculation of risk score (RS) based on the two-gene signature, patients with high RSs showed a worse prognosis. We further explored targeted drugs that could be effective in patients with a high RS by the connectivity map (CMap). Surprisingly, multiple HDAC inhibitors (HDACis) such as trichostatin A (TSA) and vorinostat (SAHA) that may have efficacy were identified. Also, we proved that HDACis could inhibit the proliferation and metastasis of NSCLC cells in vitro. Taken together, our study identified prognostic biomarkers for patients with EGFR-WT NSCLC and confirmed a novel potential role for HDACis in the clinical management of EGFR-WT patients. |
| topic |
non-small cell lung cancer histone deacetylase inhibitor WGCNA EGFR wild type metastasis proliferation |
| url |
https://www.frontiersin.org/articles/10.3389/fonc.2021.620154/full |
| work_keys_str_mv |
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| _version_ |
1724229066585800704 |
| spelling |
doaj-26d540bf9ee2403599d033445e7801832021-03-08T06:43:40ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-03-011110.3389/fonc.2021.620154620154Bioinformatics-Based Identification of HDAC Inhibitors as Potential Drugs to Target EGFR Wild-Type Non-Small-Cell Lung CancerYizhe Wang0Chunlei Zheng1Chunlei Zheng2Chunlei Zheng3Wenqing Lu4Wenqing Lu5Wenqing Lu6Duo Wang7Duo Wang8Duo Wang9Yang Cheng10Yang Chen11Kezuo Hou12Kezuo Hou13Kezuo Hou14Jianfei Qi15Yunpeng Liu16Yunpeng Liu17Yunpeng Liu18Xiaofang Che19Xiaofang Che20Xiaofang Che21Xuejun Hu22Department of Respiratory and Infectious Disease of Geriatrics, The First Hospital of China Medical University, Shenyang, ChinaDepartment of Medical Oncology, The First Hospital of China Medical University, Shenyang, ChinaKey Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, ChinaLiaoning Province Clinical Research Center for Cancer, Shenyang, ChinaDepartment of Medical Oncology, The First Hospital of China Medical University, Shenyang, ChinaKey Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, ChinaLiaoning Province Clinical Research Center for Cancer, Shenyang, ChinaDepartment of Medical Oncology, The First Hospital of China Medical University, Shenyang, ChinaKey Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, ChinaLiaoning Province Clinical Research Center for Cancer, Shenyang, ChinaDepartment of Respiratory and Infectious Disease of Geriatrics, The First Hospital of China Medical University, Shenyang, ChinaDepartment of Respiratory and Infectious Disease of Geriatrics, The First Hospital of China Medical University, Shenyang, ChinaDepartment of Medical Oncology, The First Hospital of China Medical University, Shenyang, ChinaKey Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, ChinaLiaoning Province Clinical Research Center for Cancer, Shenyang, ChinaMarlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, Baltimore, MD, United StatesDepartment of Medical Oncology, The First Hospital of China Medical University, Shenyang, ChinaKey Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, ChinaLiaoning Province Clinical Research Center for Cancer, Shenyang, ChinaDepartment of Medical Oncology, The First Hospital of China Medical University, Shenyang, ChinaKey Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, ChinaLiaoning Province Clinical Research Center for Cancer, Shenyang, ChinaDepartment of Respiratory and Infectious Disease of Geriatrics, The First Hospital of China Medical University, Shenyang, ChinaPatients with EGFR-mutant non-small-cell lung cancer (NSCLC) greatly benefit from EGFR-tyrosine kinase inhibitors (EGFR-TKIs) while the prognosis of patients who lack EGFR-sensitive mutations (EGFR wild type, EGFR-WT) remains poor due to a lack of effective therapeutic strategies. There is an urgent need to explore the key genes that affect the prognosis and develop potentially effective drugs in EGFR-WT NSCLC patients. In this study, we clustered functional modules related to the survival traits of EGFR-WT patients using weighted gene co-expression network analysis (WGCNA). We used these data to establish a two-gene prognostic signature based on the expression of CYP11B1 and DNALI1 by combining the least absolute shrinkage and selection operator (LASSO) algorithms and Cox proportional hazards regression analysis. Following the calculation of risk score (RS) based on the two-gene signature, patients with high RSs showed a worse prognosis. We further explored targeted drugs that could be effective in patients with a high RS by the connectivity map (CMap). Surprisingly, multiple HDAC inhibitors (HDACis) such as trichostatin A (TSA) and vorinostat (SAHA) that may have efficacy were identified. Also, we proved that HDACis could inhibit the proliferation and metastasis of NSCLC cells in vitro. Taken together, our study identified prognostic biomarkers for patients with EGFR-WT NSCLC and confirmed a novel potential role for HDACis in the clinical management of EGFR-WT patients.https://www.frontiersin.org/articles/10.3389/fonc.2021.620154/fullnon-small cell lung cancerhistone deacetylase inhibitorWGCNAEGFR wild typemetastasisproliferation |