A PARP1-related prognostic signature constructing and PARP-1 inhibitors screening for glioma
The current standard treatments of glioma include surgical resection, supplemented with radiotherapy and chemotherapy, but the prognosis is poor. PARP-1 (Poly ADP-ribose polymerase 1) is a hot spot for cancer-targeted therapy and was reported to be significantly elevated in glioma. In this study, we...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.916415/full |
| _version_ | 1818513358209417216 |
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| author | Hui Li Hui Li Zhenhua Wang Yuanyuan Hou Jianxin Xi Zhenqiang He Han Lu Zhishan Du Sheng Zhong Qunying Yang |
| author_facet | Hui Li Hui Li Zhenhua Wang Yuanyuan Hou Jianxin Xi Zhenqiang He Han Lu Zhishan Du Sheng Zhong Qunying Yang |
| author_sort | Hui Li |
| collection | DOAJ |
| description | The current standard treatments of glioma include surgical resection, supplemented with radiotherapy and chemotherapy, but the prognosis is poor. PARP-1 (Poly ADP-ribose polymerase 1) is a hot spot for cancer-targeted therapy and was reported to be significantly elevated in glioma. In this study, we analyzed the role of PARP-1 in DNA damage repair, constructed a PARP1-related DNA-repair prognostic signature (DPS), and screened targeted drugs for glioma. RNA-seq data of 639 glioma samples were downloaded from the GEO (Gene Expression Omnibus) database and divided into PARP1_H and PARP1_L according to the front and rear thirds of the expression level of PARP-1. First, we systematically analyzed the influence of PARP-1 on DNA damage repair, prognosis, and chemoradiotherapy sensitization of glioma. All glioma patients and patients with radiotherapy or chemotherapy had a better prognosis in PARP1_L than in PARP1_H. Next, differentially expressed DNA-repair related genes (DEGs) were identified between PARP1_H and PARP1_L by LASSO (Least Absolute Shrinkage and Selection Operator) Cox analysis and applied for constructing DPS. Based on the four-gene DPS, we then developed a new nomogram to assess overall survival in glioma patients. Additionally, PARP-1 was proved an effective target for glioma therapy. So, a series of computer-aided techniques, including Discovery Studio 4.5, Schrodinger, and PyMol, were applied for the virtual screening of favorable PARP-1 inhibitors. In conclusion, this study investigated the effect of PARP-1 on glioma prognosis and the sensitization effect of radiotherapy and chemotherapy, established a novel nomogram to evaluate the overall survival of glioma patients, and further explored targeted therapy for glioma. |
| first_indexed | 2024-12-11T00:00:12Z |
| format | Article |
| id | doaj.art-6d3df755ae30418b8bf5968f182ac547 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-11T00:00:12Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-6d3df755ae30418b8bf5968f182ac5472022-12-22T01:28:30ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-08-011010.3389/fcell.2022.916415916415A PARP1-related prognostic signature constructing and PARP-1 inhibitors screening for gliomaHui Li0Hui Li1Zhenhua Wang2Yuanyuan Hou3Jianxin Xi4Zhenqiang He5Han Lu6Zhishan Du7Sheng Zhong8Qunying Yang9Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, ChinaDepartment of Neurology, The First Hospital of Jilin University, Changchun, ChinaClinical College, Jilin University, Changchun, ChinaClinical College, Jilin University, Changchun, ChinaClinical College, Jilin University, Changchun, ChinaDepartment of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, ChinaClinical College, Jilin University, Changchun, ChinaClinical College, Jilin University, Changchun, ChinaDepartment of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, ChinaDepartment of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, ChinaThe current standard treatments of glioma include surgical resection, supplemented with radiotherapy and chemotherapy, but the prognosis is poor. PARP-1 (Poly ADP-ribose polymerase 1) is a hot spot for cancer-targeted therapy and was reported to be significantly elevated in glioma. In this study, we analyzed the role of PARP-1 in DNA damage repair, constructed a PARP1-related DNA-repair prognostic signature (DPS), and screened targeted drugs for glioma. RNA-seq data of 639 glioma samples were downloaded from the GEO (Gene Expression Omnibus) database and divided into PARP1_H and PARP1_L according to the front and rear thirds of the expression level of PARP-1. First, we systematically analyzed the influence of PARP-1 on DNA damage repair, prognosis, and chemoradiotherapy sensitization of glioma. All glioma patients and patients with radiotherapy or chemotherapy had a better prognosis in PARP1_L than in PARP1_H. Next, differentially expressed DNA-repair related genes (DEGs) were identified between PARP1_H and PARP1_L by LASSO (Least Absolute Shrinkage and Selection Operator) Cox analysis and applied for constructing DPS. Based on the four-gene DPS, we then developed a new nomogram to assess overall survival in glioma patients. Additionally, PARP-1 was proved an effective target for glioma therapy. So, a series of computer-aided techniques, including Discovery Studio 4.5, Schrodinger, and PyMol, were applied for the virtual screening of favorable PARP-1 inhibitors. In conclusion, this study investigated the effect of PARP-1 on glioma prognosis and the sensitization effect of radiotherapy and chemotherapy, established a novel nomogram to evaluate the overall survival of glioma patients, and further explored targeted therapy for glioma.https://www.frontiersin.org/articles/10.3389/fcell.2022.916415/fullGliomaPARP-1 (Poly ADP-ribose polymerase 1)DNA damage repairInhibitorsdrug screening |
| spellingShingle | Hui Li Hui Li Zhenhua Wang Yuanyuan Hou Jianxin Xi Zhenqiang He Han Lu Zhishan Du Sheng Zhong Qunying Yang A PARP1-related prognostic signature constructing and PARP-1 inhibitors screening for glioma Frontiers in Cell and Developmental Biology Glioma PARP-1 (Poly ADP-ribose polymerase 1) DNA damage repair Inhibitors drug screening |
| title | A PARP1-related prognostic signature constructing and PARP-1 inhibitors screening for glioma |
| title_full | A PARP1-related prognostic signature constructing and PARP-1 inhibitors screening for glioma |
| title_fullStr | A PARP1-related prognostic signature constructing and PARP-1 inhibitors screening for glioma |
| title_full_unstemmed | A PARP1-related prognostic signature constructing and PARP-1 inhibitors screening for glioma |
| title_short | A PARP1-related prognostic signature constructing and PARP-1 inhibitors screening for glioma |
| title_sort | parp1 related prognostic signature constructing and parp 1 inhibitors screening for glioma |
| topic | Glioma PARP-1 (Poly ADP-ribose polymerase 1) DNA damage repair Inhibitors drug screening |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.916415/full |
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