Expression pattern of cancer-associated cellular senescence genes in clear cell renal cell carcinoma distinguishes tumor subclasses with clinical implications
Abstract Clear cell renal cell carcinoma (ccRCC) is a highly lethal subtype of renal cancer. Accumulating evidence suggests cellular senescence impacts tumor development and progression. This study aimed to identify ccRCC subtypes based on a cellular senescence gene signature and assess their clinic...
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Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-84620-9 |
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| author | Zhongxu Zhu Qi Cao Jingyue Chen Yiyang Sun Fang Liu Jiang Li Miaomiao Tan |
| author_facet | Zhongxu Zhu Qi Cao Jingyue Chen Yiyang Sun Fang Liu Jiang Li Miaomiao Tan |
| author_sort | Zhongxu Zhu |
| collection | DOAJ |
| description | Abstract Clear cell renal cell carcinoma (ccRCC) is a highly lethal subtype of renal cancer. Accumulating evidence suggests cellular senescence impacts tumor development and progression. This study aimed to identify ccRCC subtypes based on a cellular senescence gene signature and assess their clinical relevance. Using hierarchical clustering on the TCGA-KIRC dataset, two senescence-related subtypes were identified and validated in independent datasets. These subtypes exhibited distinct dysregulation of cancer-related pathways, including the p53 pathway. The C2 subtype was associated with poorer overall survival, higher tumor grade and stage, low hemoglobin, and elevated platelet and serum calcium levels. Patients with the C2 subtype also had lower endothelial cell infiltration, indicating reduced benefit from anti-PD-1 immunotherapy. A nomogram based on these subtypes effectively predicted 1-, 3-, and 5-year survival outcomes. These findings highlight two distinct senescence-related ccRCC subtypes that correlate with prognosis and therapy response, offering insights for personalized treatment strategies. |
| format | Article |
| id | doaj-art-052539714dbf4ad8bec1d5c2ed7a6ae7 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-052539714dbf4ad8bec1d5c2ed7a6ae72025-01-05T12:13:28ZengNature PortfolioScientific Reports2045-23222025-01-0115111310.1038/s41598-024-84620-9Expression pattern of cancer-associated cellular senescence genes in clear cell renal cell carcinoma distinguishes tumor subclasses with clinical implicationsZhongxu Zhu0Qi Cao1Jingyue Chen2Yiyang Sun3Fang Liu4Jiang Li5Miaomiao Tan6Biomics Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of SciencesBiomics Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhou Institute for Advanced Study, University of Chinese Academy of SciencesMEDx Translational Medicine Co., LtdShanxian Vocational Secondary School of ShandongClinical Big Data Research Center, The Seventh Affiliated Hospital, Sun Yat-Sen UniversityKey Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Institute of Translational Medicine, Zhejiang Shuren UniversityAbstract Clear cell renal cell carcinoma (ccRCC) is a highly lethal subtype of renal cancer. Accumulating evidence suggests cellular senescence impacts tumor development and progression. This study aimed to identify ccRCC subtypes based on a cellular senescence gene signature and assess their clinical relevance. Using hierarchical clustering on the TCGA-KIRC dataset, two senescence-related subtypes were identified and validated in independent datasets. These subtypes exhibited distinct dysregulation of cancer-related pathways, including the p53 pathway. The C2 subtype was associated with poorer overall survival, higher tumor grade and stage, low hemoglobin, and elevated platelet and serum calcium levels. Patients with the C2 subtype also had lower endothelial cell infiltration, indicating reduced benefit from anti-PD-1 immunotherapy. A nomogram based on these subtypes effectively predicted 1-, 3-, and 5-year survival outcomes. These findings highlight two distinct senescence-related ccRCC subtypes that correlate with prognosis and therapy response, offering insights for personalized treatment strategies.https://doi.org/10.1038/s41598-024-84620-9Clear cell renal cell carcinoma (ccRCC)Cellular senescenceCancer subtypesTumor microenvironmentsTherapy response |
| spellingShingle | Zhongxu Zhu Qi Cao Jingyue Chen Yiyang Sun Fang Liu Jiang Li Miaomiao Tan Expression pattern of cancer-associated cellular senescence genes in clear cell renal cell carcinoma distinguishes tumor subclasses with clinical implications Scientific Reports Clear cell renal cell carcinoma (ccRCC) Cellular senescence Cancer subtypes Tumor microenvironments Therapy response |
| title | Expression pattern of cancer-associated cellular senescence genes in clear cell renal cell carcinoma distinguishes tumor subclasses with clinical implications |
| title_full | Expression pattern of cancer-associated cellular senescence genes in clear cell renal cell carcinoma distinguishes tumor subclasses with clinical implications |
| title_fullStr | Expression pattern of cancer-associated cellular senescence genes in clear cell renal cell carcinoma distinguishes tumor subclasses with clinical implications |
| title_full_unstemmed | Expression pattern of cancer-associated cellular senescence genes in clear cell renal cell carcinoma distinguishes tumor subclasses with clinical implications |
| title_short | Expression pattern of cancer-associated cellular senescence genes in clear cell renal cell carcinoma distinguishes tumor subclasses with clinical implications |
| title_sort | expression pattern of cancer associated cellular senescence genes in clear cell renal cell carcinoma distinguishes tumor subclasses with clinical implications |
| topic | Clear cell renal cell carcinoma (ccRCC) Cellular senescence Cancer subtypes Tumor microenvironments Therapy response |
| url | https://doi.org/10.1038/s41598-024-84620-9 |
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