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Predictive value of RAD51 on the survival and drug responsiveness of ovarian cancer
BACKGROUND: Ovarian cancer has greatly endangered and deteriorated female health conditions worldwide. Refinement of predictive biomarkers could enable patient stratification and help optimize disease management. METHODS: RAD51 expression profile, target-disease associations, and fitness scores of R...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097773/ https://www.ncbi.nlm.nih.gov/pubmed/33952262 http://dx.doi.org/10.1186/s12935-021-01953-5 |
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author | Feng, Yuchen Wang, Daoqi Xiong, Luyang Zhen, Guohua Tan, Jiahong |
author_facet | Feng, Yuchen Wang, Daoqi Xiong, Luyang Zhen, Guohua Tan, Jiahong |
author_sort | Feng, Yuchen |
collection | PubMed |
description | BACKGROUND: Ovarian cancer has greatly endangered and deteriorated female health conditions worldwide. Refinement of predictive biomarkers could enable patient stratification and help optimize disease management. METHODS: RAD51 expression profile, target-disease associations, and fitness scores of RAD51 were analyzed in ovarian cancer using bioinformatic analysis. To further identify its role, gene enrichment analysis was performed, and a regulatory network was constructed. Survival analysis and drug sensitivity assay were performed to evaluate the effect of RAD51 expression on ovarian cancer prognosis. The predictive value of RAD51 was then confirmed in a validation cohort immunohistochemically. RESULTS: Ovarian cancer expressed more RAD51 than normal ovary. RAD51 conferred ovarian cancer dependency and was associated with ovarian cancer. RAD51 had extensive target-disease associations with various diseases, including ovarian cancer. Genes that correlate with and interact with RAD51 were involved in DNA damage repair and drug responsiveness. High RAD51 expression indicated unfavorable survival outcomes and resistance to platinum, taxane, and PARP inhibitors in ovarian cancer. In the validation cohort (126 patients), high RAD51 expression indicated platinum resistance, and platinum-resistant patients expressed more RAD51. Patients with high RAD51 expression had shorter OS (HR = 2.968, P < 0.0001) and poorer PFS (HR = 2.838, P < 0.0001). RAD51 expression level was negatively correlated with patients’ survival length. CONCLUSIONS: Ovarian cancer had pronounced RAD51 expression and RAD51 conferred ovarian cancer dependency. High RAD51 expression indicated poor survival and decreased drug sensitivity. RAD51 has predictive value in ovarian cancer and can be exploited as a predictive biomarker. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-01953-5. |
format | Online Article Text |
id | pubmed-8097773 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-80977732021-05-05 Predictive value of RAD51 on the survival and drug responsiveness of ovarian cancer Feng, Yuchen Wang, Daoqi Xiong, Luyang Zhen, Guohua Tan, Jiahong Cancer Cell Int Primary Research BACKGROUND: Ovarian cancer has greatly endangered and deteriorated female health conditions worldwide. Refinement of predictive biomarkers could enable patient stratification and help optimize disease management. METHODS: RAD51 expression profile, target-disease associations, and fitness scores of RAD51 were analyzed in ovarian cancer using bioinformatic analysis. To further identify its role, gene enrichment analysis was performed, and a regulatory network was constructed. Survival analysis and drug sensitivity assay were performed to evaluate the effect of RAD51 expression on ovarian cancer prognosis. The predictive value of RAD51 was then confirmed in a validation cohort immunohistochemically. RESULTS: Ovarian cancer expressed more RAD51 than normal ovary. RAD51 conferred ovarian cancer dependency and was associated with ovarian cancer. RAD51 had extensive target-disease associations with various diseases, including ovarian cancer. Genes that correlate with and interact with RAD51 were involved in DNA damage repair and drug responsiveness. High RAD51 expression indicated unfavorable survival outcomes and resistance to platinum, taxane, and PARP inhibitors in ovarian cancer. In the validation cohort (126 patients), high RAD51 expression indicated platinum resistance, and platinum-resistant patients expressed more RAD51. Patients with high RAD51 expression had shorter OS (HR = 2.968, P < 0.0001) and poorer PFS (HR = 2.838, P < 0.0001). RAD51 expression level was negatively correlated with patients’ survival length. CONCLUSIONS: Ovarian cancer had pronounced RAD51 expression and RAD51 conferred ovarian cancer dependency. High RAD51 expression indicated poor survival and decreased drug sensitivity. RAD51 has predictive value in ovarian cancer and can be exploited as a predictive biomarker. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-01953-5. BioMed Central 2021-05-05 /pmc/articles/PMC8097773/ /pubmed/33952262 http://dx.doi.org/10.1186/s12935-021-01953-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Primary Research Feng, Yuchen Wang, Daoqi Xiong, Luyang Zhen, Guohua Tan, Jiahong Predictive value of RAD51 on the survival and drug responsiveness of ovarian cancer |
title | Predictive value of RAD51 on the survival and drug responsiveness of ovarian cancer |
title_full | Predictive value of RAD51 on the survival and drug responsiveness of ovarian cancer |
title_fullStr | Predictive value of RAD51 on the survival and drug responsiveness of ovarian cancer |
title_full_unstemmed | Predictive value of RAD51 on the survival and drug responsiveness of ovarian cancer |
title_short | Predictive value of RAD51 on the survival and drug responsiveness of ovarian cancer |
title_sort | predictive value of rad51 on the survival and drug responsiveness of ovarian cancer |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097773/ https://www.ncbi.nlm.nih.gov/pubmed/33952262 http://dx.doi.org/10.1186/s12935-021-01953-5 |
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