Comprehensive analysis to identify the RP11–478C19.2/ E2F7 axis as a novel biomarker for treatment decisions in clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC), accounting for 70–80% of all renal cell carcinomas, is a common malignancy. Survival rates decrease significantly in patients with advanced and metastatic ccRCC. Furthermore, ccRCC is less responsive to radiation and chemotherapy than other cancers. Therefore...

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Main Authors: Kai Zeng, Guoda Song, Bingliang Chen, Xintao Gao, Chaofan Liu, Jianping Miao, Yajun Ruan, Yang Luan, Xin Chen, Jihong Liu, Qinyu Li, Bo Liu
Format: Article
Language:English
Published: Elsevier 2022-11-01
Series:Translational Oncology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S193652332200184X
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author Kai Zeng
Guoda Song
Bingliang Chen
Xintao Gao
Chaofan Liu
Jianping Miao
Yajun Ruan
Yang Luan
Xin Chen
Jihong Liu
Qinyu Li
Bo Liu
author_facet Kai Zeng
Guoda Song
Bingliang Chen
Xintao Gao
Chaofan Liu
Jianping Miao
Yajun Ruan
Yang Luan
Xin Chen
Jihong Liu
Qinyu Li
Bo Liu
author_sort Kai Zeng
collection DOAJ
description Clear cell renal cell carcinoma (ccRCC), accounting for 70–80% of all renal cell carcinomas, is a common malignancy. Survival rates decrease significantly in patients with advanced and metastatic ccRCC. Furthermore, ccRCC is less responsive to radiation and chemotherapy than other cancers. Therefore, targeted therapy and immunotherapy are particularly important for ccRCC management. A growing body of literature recognizes that competitive endogenous RNA (ceRNA) regulatory networks play a crucial role in various cancers. However, the biological functions of the ceRNA network in ccRCC require further investigation. In this study, we built the ceRNA network for ccRCC using the “GDCRNATools” package. After survival analysis, the RP11–478C19.2/hsa-miR-181b-5p, hsa-miR-181a-5p, and hsa-miR-181c-5p/E2F7 axes were obtained for further analysis. Unsupervised clustering was conducted basing on this ceRNA network. The results indicated that the prognosis and immune infiltration levels differed between the two clusters. Furthermore, we conducted correlation analysis, immune infiltration analysis, tumor mutation burden analysis, GSEA analysis, drug sensitivity analysis and pan-cancer analysis of E2F7 to explore its potential role in oncogenesis. Experiments in vitro were performed to confirm the pro-oncogenic impact of E2F7. The results suggest that the RP11–478C19.2/E2F7 axis might be a biomarker for the inclusion of cabozantinib, pazopanib, sunitinib, and immunotherapy in the therapeutic regimen. In summary, we found that the ceRNA-based RP11–478C19.2/E2F7 axis is involved in ccRCC and that it could be a novel biomarker for treatment decisions and a possible therapeutic target to increase the success of targeted therapy and immunotherapy in ccRCC.
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spelling doaj.art-4d1f4adb78be424d9bd27f036430a6722022-12-22T03:08:38ZengElsevierTranslational Oncology1936-52332022-11-0125101525Comprehensive analysis to identify the RP11–478C19.2/ E2F7 axis as a novel biomarker for treatment decisions in clear cell renal cell carcinomaKai Zeng0Guoda Song1Bingliang Chen2Xintao Gao3Chaofan Liu4Jianping Miao5Yajun Ruan6Yang Luan7Xin Chen8Jihong Liu9Qinyu Li10Bo Liu11Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, ChinaDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, ChinaDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, ChinaDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, ChinaDepartment of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, ChinaDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, ChinaDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, ChinaDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, ChinaDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China; Corresponding authors.Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China; Corresponding authors.Clear cell renal cell carcinoma (ccRCC), accounting for 70–80% of all renal cell carcinomas, is a common malignancy. Survival rates decrease significantly in patients with advanced and metastatic ccRCC. Furthermore, ccRCC is less responsive to radiation and chemotherapy than other cancers. Therefore, targeted therapy and immunotherapy are particularly important for ccRCC management. A growing body of literature recognizes that competitive endogenous RNA (ceRNA) regulatory networks play a crucial role in various cancers. However, the biological functions of the ceRNA network in ccRCC require further investigation. In this study, we built the ceRNA network for ccRCC using the “GDCRNATools” package. After survival analysis, the RP11–478C19.2/hsa-miR-181b-5p, hsa-miR-181a-5p, and hsa-miR-181c-5p/E2F7 axes were obtained for further analysis. Unsupervised clustering was conducted basing on this ceRNA network. The results indicated that the prognosis and immune infiltration levels differed between the two clusters. Furthermore, we conducted correlation analysis, immune infiltration analysis, tumor mutation burden analysis, GSEA analysis, drug sensitivity analysis and pan-cancer analysis of E2F7 to explore its potential role in oncogenesis. Experiments in vitro were performed to confirm the pro-oncogenic impact of E2F7. The results suggest that the RP11–478C19.2/E2F7 axis might be a biomarker for the inclusion of cabozantinib, pazopanib, sunitinib, and immunotherapy in the therapeutic regimen. In summary, we found that the ceRNA-based RP11–478C19.2/E2F7 axis is involved in ccRCC and that it could be a novel biomarker for treatment decisions and a possible therapeutic target to increase the success of targeted therapy and immunotherapy in ccRCC.http://www.sciencedirect.com/science/article/pii/S193652332200184XCompeting endogenous RNAsE2F7Immune infiltration analysisccRCCTreatment decisionPan-cancer analysis
spellingShingle Kai Zeng
Guoda Song
Bingliang Chen
Xintao Gao
Chaofan Liu
Jianping Miao
Yajun Ruan
Yang Luan
Xin Chen
Jihong Liu
Qinyu Li
Bo Liu
Comprehensive analysis to identify the RP11–478C19.2/ E2F7 axis as a novel biomarker for treatment decisions in clear cell renal cell carcinoma
Translational Oncology
Competing endogenous RNAs
E2F7
Immune infiltration analysis
ccRCC
Treatment decision
Pan-cancer analysis
title Comprehensive analysis to identify the RP11–478C19.2/ E2F7 axis as a novel biomarker for treatment decisions in clear cell renal cell carcinoma
title_full Comprehensive analysis to identify the RP11–478C19.2/ E2F7 axis as a novel biomarker for treatment decisions in clear cell renal cell carcinoma
title_fullStr Comprehensive analysis to identify the RP11–478C19.2/ E2F7 axis as a novel biomarker for treatment decisions in clear cell renal cell carcinoma
title_full_unstemmed Comprehensive analysis to identify the RP11–478C19.2/ E2F7 axis as a novel biomarker for treatment decisions in clear cell renal cell carcinoma
title_short Comprehensive analysis to identify the RP11–478C19.2/ E2F7 axis as a novel biomarker for treatment decisions in clear cell renal cell carcinoma
title_sort comprehensive analysis to identify the rp11 478c19 2 e2f7 axis as a novel biomarker for treatment decisions in clear cell renal cell carcinoma
topic Competing endogenous RNAs
E2F7
Immune infiltration analysis
ccRCC
Treatment decision
Pan-cancer analysis
url http://www.sciencedirect.com/science/article/pii/S193652332200184X
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