Identification of a dysregulated CircRNA-associated gene signature for predicting prognosis, immune landscape, and drug candidates in bladder cancer
Increasing evidences have demonstrated that circular RNA (circRNAs) plays a an essential regulatory role in initiation, progression and immunotherapy resistance of various cancers. However, circRNAs have rarely been studied in bladder cancer (BCa). The purpose of this research is to explore new circ...
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.1018285/full |
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| author | Chong Shen Chong Shen Zhi Li Zhi Li Yinglang Zhang Yinglang Zhang Zhe Zhang Zhe Zhang Zhouliang Wu Zhouliang Wu La Da La Da Shaobo Yang Shaobo Yang Zejin Wang Zejin Wang Yu Zhang Yu Zhang Yunkai Qie Yunkai Qie Gangjian Zhao Gangjian Zhao Yuda Lin Yuda Lin Shiwang Huang Shiwang Huang Mingli Zhou Hailong Hu Hailong Hu |
| author_facet | Chong Shen Chong Shen Zhi Li Zhi Li Yinglang Zhang Yinglang Zhang Zhe Zhang Zhe Zhang Zhouliang Wu Zhouliang Wu La Da La Da Shaobo Yang Shaobo Yang Zejin Wang Zejin Wang Yu Zhang Yu Zhang Yunkai Qie Yunkai Qie Gangjian Zhao Gangjian Zhao Yuda Lin Yuda Lin Shiwang Huang Shiwang Huang Mingli Zhou Hailong Hu Hailong Hu |
| author_sort | Chong Shen |
| collection | DOAJ |
| description | Increasing evidences have demonstrated that circular RNA (circRNAs) plays a an essential regulatory role in initiation, progression and immunotherapy resistance of various cancers. However, circRNAs have rarely been studied in bladder cancer (BCa). The purpose of this research is to explore new circRNAs and their potential mechanisms in BCa. A novel ceRNA-regulated network, including 87 differentially expressed circRNAs (DE-circRNAs), 126 DE-miRNAs, and 217 DE-mRNAs was constructed to better understanding the biological processes using Cytoscape 3.7.1 based on our previously high-throughput circRNA sequencing and five GEO datasets. Subsequently, five randomly selected circRNAs (upregulated circ_0001681; downregulated circ_0000643, circ_0001798, circ_0006117 and circ_0067900) in 20 pairs of BCa and paracancerous tissues were confirmed using qRT-PCR. Functional analysis results determined that 772 GO functions and 32 KEGG pathways were enriched in the ceRNA network. Ten genes (PFKFB4, EDNRA, GSN, GAS1, PAPPA, DTL, TGFBI, PRSS8, RGS1 and TCF4) were selected for signature construction among the ceRNA network. The Human Protein Atlas (HPA) expression of these genes were consistent with the above sequencing data. Notably, the model was validated in multiple external datasets (GSE13507, GSE31684, GSE48075, IMvigor210 and GSE32894). The immune-infiltration was evaluated by 7 published algorithms (i.e., TIMER, CIBERSORT, CIBERSORT-ABS, QUANTISEQ, MCPCOUNTER, XCELL and EPIC). Next, Correlations between riskscore or risk groups and clinicopathological data, overall survival, recognized immunoregulatory cells or common chemotherapeutic agents of BCa patients were performed using wilcox rank test, chi-square test, cox regression and spearman’s correlation analysis; and, these results are significant. According to R package “GSVA” and “clusterProfiler”, the most significantly enriched HALLMARK and KEGG pathway was separately the ‘Epithelial Mesenchymal Transition’ and ‘Ecm Receptor Interaction’ in the high- vs. low-risk group. Additionally, the functional experiments in vitro also revealed that the overexpression of has_circ_0067900 significantly impaired the proliferation, migration, and invasion capacities of BCa cells. Collectively, the results of the current study provide a novel landscape of circRNA-associated ceRNA-regulated network in BCa. The ceRNA-associated gene model which was constructed presented a high predictive performance for the prognosis, immunotherapeutic responsiveness, and chemotherapeutic sensitivity of BCa. And, has_circ_0067900 was originally proposed as tumor suppressor for patients with BCa. |
| first_indexed | 2024-04-13T22:41:29Z |
| format | Article |
| id | doaj.art-0149e5ae08f64a3d8773d3db977d47fb |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-13T22:41:29Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-0149e5ae08f64a3d8773d3db977d47fb2022-12-22T02:26:36ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-10-011210.3389/fonc.2022.10182851018285Identification of a dysregulated CircRNA-associated gene signature for predicting prognosis, immune landscape, and drug candidates in bladder cancerChong Shen0Chong Shen1Zhi Li2Zhi Li3Yinglang Zhang4Yinglang Zhang5Zhe Zhang6Zhe Zhang7Zhouliang Wu8Zhouliang Wu9La Da10La Da11Shaobo Yang12Shaobo Yang13Zejin Wang14Zejin Wang15Yu Zhang16Yu Zhang17Yunkai Qie18Yunkai Qie19Gangjian Zhao20Gangjian Zhao21Yuda Lin22Yuda Lin23Shiwang Huang24Shiwang Huang25Mingli Zhou26Hailong Hu27Hailong Hu28Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, ChinaDepartment of Urology, The Second Hospital of Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, ChinaDepartment of Urology, The Second Hospital of Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, ChinaDepartment of Urology, The Second Hospital of Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, ChinaDepartment of Urology, The Second Hospital of Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, ChinaDepartment of Urology, The Second Hospital of Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, ChinaDepartment of Urology, The Second Hospital of Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, ChinaDepartment of Urology, The Second Hospital of Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, ChinaDepartment of Urology, The Second Hospital of Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, ChinaDepartment of Urology, The Second Hospital of Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, ChinaDepartment of Urology, The Second Hospital of Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, ChinaDepartment of Urology, The Second Hospital of Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, ChinaDepartment of Urology, The Second Hospital of Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, ChinaDepartment of Neuromuscular Diseases, Third Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Urology, The Second Hospital of Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, ChinaIncreasing evidences have demonstrated that circular RNA (circRNAs) plays a an essential regulatory role in initiation, progression and immunotherapy resistance of various cancers. However, circRNAs have rarely been studied in bladder cancer (BCa). The purpose of this research is to explore new circRNAs and their potential mechanisms in BCa. A novel ceRNA-regulated network, including 87 differentially expressed circRNAs (DE-circRNAs), 126 DE-miRNAs, and 217 DE-mRNAs was constructed to better understanding the biological processes using Cytoscape 3.7.1 based on our previously high-throughput circRNA sequencing and five GEO datasets. Subsequently, five randomly selected circRNAs (upregulated circ_0001681; downregulated circ_0000643, circ_0001798, circ_0006117 and circ_0067900) in 20 pairs of BCa and paracancerous tissues were confirmed using qRT-PCR. Functional analysis results determined that 772 GO functions and 32 KEGG pathways were enriched in the ceRNA network. Ten genes (PFKFB4, EDNRA, GSN, GAS1, PAPPA, DTL, TGFBI, PRSS8, RGS1 and TCF4) were selected for signature construction among the ceRNA network. The Human Protein Atlas (HPA) expression of these genes were consistent with the above sequencing data. Notably, the model was validated in multiple external datasets (GSE13507, GSE31684, GSE48075, IMvigor210 and GSE32894). The immune-infiltration was evaluated by 7 published algorithms (i.e., TIMER, CIBERSORT, CIBERSORT-ABS, QUANTISEQ, MCPCOUNTER, XCELL and EPIC). Next, Correlations between riskscore or risk groups and clinicopathological data, overall survival, recognized immunoregulatory cells or common chemotherapeutic agents of BCa patients were performed using wilcox rank test, chi-square test, cox regression and spearman’s correlation analysis; and, these results are significant. According to R package “GSVA” and “clusterProfiler”, the most significantly enriched HALLMARK and KEGG pathway was separately the ‘Epithelial Mesenchymal Transition’ and ‘Ecm Receptor Interaction’ in the high- vs. low-risk group. Additionally, the functional experiments in vitro also revealed that the overexpression of has_circ_0067900 significantly impaired the proliferation, migration, and invasion capacities of BCa cells. Collectively, the results of the current study provide a novel landscape of circRNA-associated ceRNA-regulated network in BCa. The ceRNA-associated gene model which was constructed presented a high predictive performance for the prognosis, immunotherapeutic responsiveness, and chemotherapeutic sensitivity of BCa. And, has_circ_0067900 was originally proposed as tumor suppressor for patients with BCa.https://www.frontiersin.org/articles/10.3389/fonc.2022.1018285/fullbladder cancerCircRNA-related prognostic signatureimmune infiltrationimmunotherapychemotherapy |
| spellingShingle | Chong Shen Chong Shen Zhi Li Zhi Li Yinglang Zhang Yinglang Zhang Zhe Zhang Zhe Zhang Zhouliang Wu Zhouliang Wu La Da La Da Shaobo Yang Shaobo Yang Zejin Wang Zejin Wang Yu Zhang Yu Zhang Yunkai Qie Yunkai Qie Gangjian Zhao Gangjian Zhao Yuda Lin Yuda Lin Shiwang Huang Shiwang Huang Mingli Zhou Hailong Hu Hailong Hu Identification of a dysregulated CircRNA-associated gene signature for predicting prognosis, immune landscape, and drug candidates in bladder cancer Frontiers in Oncology bladder cancer CircRNA-related prognostic signature immune infiltration immunotherapy chemotherapy |
| title | Identification of a dysregulated CircRNA-associated gene signature for predicting prognosis, immune landscape, and drug candidates in bladder cancer |
| title_full | Identification of a dysregulated CircRNA-associated gene signature for predicting prognosis, immune landscape, and drug candidates in bladder cancer |
| title_fullStr | Identification of a dysregulated CircRNA-associated gene signature for predicting prognosis, immune landscape, and drug candidates in bladder cancer |
| title_full_unstemmed | Identification of a dysregulated CircRNA-associated gene signature for predicting prognosis, immune landscape, and drug candidates in bladder cancer |
| title_short | Identification of a dysregulated CircRNA-associated gene signature for predicting prognosis, immune landscape, and drug candidates in bladder cancer |
| title_sort | identification of a dysregulated circrna associated gene signature for predicting prognosis immune landscape and drug candidates in bladder cancer |
| topic | bladder cancer CircRNA-related prognostic signature immune infiltration immunotherapy chemotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.1018285/full |
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