A novel thinking: DDR axis refines the classification of ccRCC with distinctive prognosis, multi omics landscape and management strategy
BackgroundDNA damage response and repair (DDR) related signatures play an important role in maintaining genome stability and other biological processes. It also affects the occurrence, development, and treatment of cancer. However, in renal cell carcinoma (RCC), especially clear cell renal carcinoma...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Public Health |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fpubh.2022.1029509/full |
| _version_ | 1797983902707482624 |
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| author | Aimin Jiang Jiaao Song Xiao Fang Yu Fang Zheng Wang Bing Liu Zhenjie Wu Le Qu Peng Luo Linhui Wang |
| author_facet | Aimin Jiang Jiaao Song Xiao Fang Yu Fang Zheng Wang Bing Liu Zhenjie Wu Le Qu Peng Luo Linhui Wang |
| author_sort | Aimin Jiang |
| collection | DOAJ |
| description | BackgroundDNA damage response and repair (DDR) related signatures play an important role in maintaining genome stability and other biological processes. It also affects the occurrence, development, and treatment of cancer. However, in renal cell carcinoma (RCC), especially clear cell renal carcinoma (ccRCC), the potential association between DDR-related signatures and tumor heterogeneity and tumor microenvironment (TME) remains unclear.MethodsUtilizing unsupervised clustering algorithm, we divided RCC into two subgroups, DCS1 and DCS2, according to the differences in DDR gene expression, and compared the characteristics of the two subgroups through multiple dimensions.ResultsCompared with DCS1, DCS2 patients have higher clinical stage/grade and worse prognosis, which may be related to active metabolic status and immunosuppression status. At the same time, the high mutation rate in DCS2 may also be an important reason for the prognosis. We also analyzed the sensitivity of the two subgroups to different therapeutic agents and established a subtypes' biomarkers-based prognostic system with good validation results to provide ideas for clinical diagnosis and treatment. Finally, we identified a pivotal role for DDX1 in the DDR gene set, which may serve as a future therapeutic target.ConclusionThis study showed that DDR has an important impact on the development and treatment of RCC. DCS2 subtypes have a poor prognosis, and more personalized treatment and follow-up programs may be needed. The assessment of DDR gene mutations in patients may be helpful for clinical decision-making. DDX1 may be one of the effective targets for RCC treatment in the future. |
| first_indexed | 2024-04-11T06:53:30Z |
| format | Article |
| id | doaj.art-80d070a5bcb245f6a9e7fd0eeea15d84 |
| institution | Directory Open Access Journal |
| issn | 2296-2565 |
| language | English |
| last_indexed | 2024-04-11T06:53:30Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Public Health |
| spelling | doaj.art-80d070a5bcb245f6a9e7fd0eeea15d842022-12-22T04:39:05ZengFrontiers Media S.A.Frontiers in Public Health2296-25652022-11-011010.3389/fpubh.2022.10295091029509A novel thinking: DDR axis refines the classification of ccRCC with distinctive prognosis, multi omics landscape and management strategyAimin Jiang0Jiaao Song1Xiao Fang2Yu Fang3Zheng Wang4Bing Liu5Zhenjie Wu6Le Qu7Peng Luo8Linhui Wang9Department of Urology, Changhai Hospital, Navel Medical University (Second Military Medical University), Shanghai, ChinaDepartment of Urology, Changhai Hospital, Navel Medical University (Second Military Medical University), Shanghai, ChinaDepartment of Urology, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, ChinaDepartment of Urology, Changhai Hospital, Navel Medical University (Second Military Medical University), Shanghai, ChinaDepartment of Urology, Changhai Hospital, Navel Medical University (Second Military Medical University), Shanghai, ChinaDepartment of Urology, The Third Affiliated Hospital, Naval Medical University (Second Military Medical University), Shanghai, ChinaDepartment of Urology, Changhai Hospital, Navel Medical University (Second Military Medical University), Shanghai, ChinaDepartment of Urology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, ChinaDepartment of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Urology, Changhai Hospital, Navel Medical University (Second Military Medical University), Shanghai, ChinaBackgroundDNA damage response and repair (DDR) related signatures play an important role in maintaining genome stability and other biological processes. It also affects the occurrence, development, and treatment of cancer. However, in renal cell carcinoma (RCC), especially clear cell renal carcinoma (ccRCC), the potential association between DDR-related signatures and tumor heterogeneity and tumor microenvironment (TME) remains unclear.MethodsUtilizing unsupervised clustering algorithm, we divided RCC into two subgroups, DCS1 and DCS2, according to the differences in DDR gene expression, and compared the characteristics of the two subgroups through multiple dimensions.ResultsCompared with DCS1, DCS2 patients have higher clinical stage/grade and worse prognosis, which may be related to active metabolic status and immunosuppression status. At the same time, the high mutation rate in DCS2 may also be an important reason for the prognosis. We also analyzed the sensitivity of the two subgroups to different therapeutic agents and established a subtypes' biomarkers-based prognostic system with good validation results to provide ideas for clinical diagnosis and treatment. Finally, we identified a pivotal role for DDX1 in the DDR gene set, which may serve as a future therapeutic target.ConclusionThis study showed that DDR has an important impact on the development and treatment of RCC. DCS2 subtypes have a poor prognosis, and more personalized treatment and follow-up programs may be needed. The assessment of DDR gene mutations in patients may be helpful for clinical decision-making. DDX1 may be one of the effective targets for RCC treatment in the future.https://www.frontiersin.org/articles/10.3389/fpubh.2022.1029509/fullrenal cell carcinomaDNA damage responsemolecular subtypesmulti-omicsDDX1 |
| spellingShingle | Aimin Jiang Jiaao Song Xiao Fang Yu Fang Zheng Wang Bing Liu Zhenjie Wu Le Qu Peng Luo Linhui Wang A novel thinking: DDR axis refines the classification of ccRCC with distinctive prognosis, multi omics landscape and management strategy Frontiers in Public Health renal cell carcinoma DNA damage response molecular subtypes multi-omics DDX1 |
| title | A novel thinking: DDR axis refines the classification of ccRCC with distinctive prognosis, multi omics landscape and management strategy |
| title_full | A novel thinking: DDR axis refines the classification of ccRCC with distinctive prognosis, multi omics landscape and management strategy |
| title_fullStr | A novel thinking: DDR axis refines the classification of ccRCC with distinctive prognosis, multi omics landscape and management strategy |
| title_full_unstemmed | A novel thinking: DDR axis refines the classification of ccRCC with distinctive prognosis, multi omics landscape and management strategy |
| title_short | A novel thinking: DDR axis refines the classification of ccRCC with distinctive prognosis, multi omics landscape and management strategy |
| title_sort | novel thinking ddr axis refines the classification of ccrcc with distinctive prognosis multi omics landscape and management strategy |
| topic | renal cell carcinoma DNA damage response molecular subtypes multi-omics DDX1 |
| url | https://www.frontiersin.org/articles/10.3389/fpubh.2022.1029509/full |
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