Copy Number Variations of CEP63, FOSL2 and PAQR6 Serve as Novel Signatures for the Prognosis of Bladder Cancer
BackgroundFinding effective prognostic signatures is of great urgency due to the high risk of recurrence and progression of bladder cancer (BC). Although a lot of genetic alterations are involved in the carcinogenesis, none of them were referred in the current risk group stratifications. In this stu...
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.674933/full |
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| author | Zhao Cai Huang Chen Jingqiao Bai Yang Zheng Jianhui Ma Xiongwei Cai Yu Liu Kaitai Zhang Jianzhong Shou Yanning Gao |
| author_facet | Zhao Cai Huang Chen Jingqiao Bai Yang Zheng Jianhui Ma Xiongwei Cai Yu Liu Kaitai Zhang Jianzhong Shou Yanning Gao |
| author_sort | Zhao Cai |
| collection | DOAJ |
| description | BackgroundFinding effective prognostic signatures is of great urgency due to the high risk of recurrence and progression of bladder cancer (BC). Although a lot of genetic alterations are involved in the carcinogenesis, none of them were referred in the current risk group stratifications. In this study, we aimed to find significant copy number variations (CNVs) to predict prognosis for BC patients.MethodsCNVs with high aberration frequencies in BC were explored by array-based comparative genomic hybridization in 65 tumor samples. Candidates were validated in independent groups of BC tumor samples (n=219) and urine samples (n=123). 3D digital PCR was applied for detecting accurate gene copy numbers in BC urine. In order to explore the prognostic value of candidate CNVs, all enrolled patients were followed up for the disease-free survival (DFS). Cox proportional hazards regression analysis was performed to find the independent prognostic factors for DFS.ResultsCNVs of CEP63, FOSL2 and PAQR6 with high aberration frequencies (67.7%, 56.9% and 60.0%, respectively) were found in BC tumors. Copy numbers of CEP63, FOSL2 and PAQR6 were gained in 219 tumor samples. CNVs of CEP63 and FOSL2 were correlated with advanced tumor stage and high grade. Retrospective analysis (median follow-up time: 69 months) revealed that CNVs of CEP63 and FOSL2 were independent prognostic factors for DFS of non-muscle-invasive bladder cancer (NMIBC) patients, while CNVs of FOSL2 and PAQR6 were independent prognostic factors for DFS of muscle-invasive bladder cancer (MIBC) patients. Models for predicting DFS were constructed based on CNVs of three genes. Patients with high prognostic indexes tended to have poor DFS. Prognostic index can also help to identify those with worse outcomes among high risk NMIBC patients. Copy number gains of CEP63 and FOSL2 in urine were found to be significantly correlated with poor DFS of NMIBC patients.ConclusionsCNVs of CEP63, FOSL2 and PAQR6 were capable of predicting DFS and may serve as promising signatures for prognosis of BC. |
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| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-18T00:36:45Z |
| publishDate | 2021-05-01 |
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| series | Frontiers in Oncology |
| spelling | doaj.art-c08bf59d655940f5b183bec85b018f822022-12-21T21:27:00ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-05-011110.3389/fonc.2021.674933674933Copy Number Variations of CEP63, FOSL2 and PAQR6 Serve as Novel Signatures for the Prognosis of Bladder CancerZhao Cai0Huang Chen1Jingqiao Bai2Yang Zheng3Jianhui Ma4Xiongwei Cai5Yu Liu6Kaitai Zhang7Jianzhong Shou8Yanning Gao9State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Pathology, China-Japan Friendship Hospital, Beijing, ChinaState Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaState Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaState Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaState Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaState Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaState Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBackgroundFinding effective prognostic signatures is of great urgency due to the high risk of recurrence and progression of bladder cancer (BC). Although a lot of genetic alterations are involved in the carcinogenesis, none of them were referred in the current risk group stratifications. In this study, we aimed to find significant copy number variations (CNVs) to predict prognosis for BC patients.MethodsCNVs with high aberration frequencies in BC were explored by array-based comparative genomic hybridization in 65 tumor samples. Candidates were validated in independent groups of BC tumor samples (n=219) and urine samples (n=123). 3D digital PCR was applied for detecting accurate gene copy numbers in BC urine. In order to explore the prognostic value of candidate CNVs, all enrolled patients were followed up for the disease-free survival (DFS). Cox proportional hazards regression analysis was performed to find the independent prognostic factors for DFS.ResultsCNVs of CEP63, FOSL2 and PAQR6 with high aberration frequencies (67.7%, 56.9% and 60.0%, respectively) were found in BC tumors. Copy numbers of CEP63, FOSL2 and PAQR6 were gained in 219 tumor samples. CNVs of CEP63 and FOSL2 were correlated with advanced tumor stage and high grade. Retrospective analysis (median follow-up time: 69 months) revealed that CNVs of CEP63 and FOSL2 were independent prognostic factors for DFS of non-muscle-invasive bladder cancer (NMIBC) patients, while CNVs of FOSL2 and PAQR6 were independent prognostic factors for DFS of muscle-invasive bladder cancer (MIBC) patients. Models for predicting DFS were constructed based on CNVs of three genes. Patients with high prognostic indexes tended to have poor DFS. Prognostic index can also help to identify those with worse outcomes among high risk NMIBC patients. Copy number gains of CEP63 and FOSL2 in urine were found to be significantly correlated with poor DFS of NMIBC patients.ConclusionsCNVs of CEP63, FOSL2 and PAQR6 were capable of predicting DFS and may serve as promising signatures for prognosis of BC.https://www.frontiersin.org/articles/10.3389/fonc.2021.674933/fullcopy number variationbladder cancerprognosisCEP63FOSL2PAQR6 |
| spellingShingle | Zhao Cai Huang Chen Jingqiao Bai Yang Zheng Jianhui Ma Xiongwei Cai Yu Liu Kaitai Zhang Jianzhong Shou Yanning Gao Copy Number Variations of CEP63, FOSL2 and PAQR6 Serve as Novel Signatures for the Prognosis of Bladder Cancer Frontiers in Oncology copy number variation bladder cancer prognosis CEP63 FOSL2 PAQR6 |
| title | Copy Number Variations of CEP63, FOSL2 and PAQR6 Serve as Novel Signatures for the Prognosis of Bladder Cancer |
| title_full | Copy Number Variations of CEP63, FOSL2 and PAQR6 Serve as Novel Signatures for the Prognosis of Bladder Cancer |
| title_fullStr | Copy Number Variations of CEP63, FOSL2 and PAQR6 Serve as Novel Signatures for the Prognosis of Bladder Cancer |
| title_full_unstemmed | Copy Number Variations of CEP63, FOSL2 and PAQR6 Serve as Novel Signatures for the Prognosis of Bladder Cancer |
| title_short | Copy Number Variations of CEP63, FOSL2 and PAQR6 Serve as Novel Signatures for the Prognosis of Bladder Cancer |
| title_sort | copy number variations of cep63 fosl2 and paqr6 serve as novel signatures for the prognosis of bladder cancer |
| topic | copy number variation bladder cancer prognosis CEP63 FOSL2 PAQR6 |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.674933/full |
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