The molecular characteristics of DNA damage and repair related to P53 mutation for predicting the recurrence and immunotherapy response in hepatocellular carcinoma
Abstract Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths globally, owing to its high recurrence rate of 50 to 70% within five years. Despite known associations of certain DNA damage and repair (DDR) genes with tumor recurrence and drug resistance, a comprehensive...
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Nature Portfolio
2025-04-01
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| Online Access: | https://doi.org/10.1038/s41598-025-99853-5 |
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| author | Jiayao Ma Diya Tang Guangzu Cui Xiangyang Zhang Xinwen Wang Yin Li Erya Hu Xin Zhou Haicong Liu Qingping Peng Changjing Cai Xiangying Deng Shan Zeng Yihong Chen Zemin Xiao |
| author_facet | Jiayao Ma Diya Tang Guangzu Cui Xiangyang Zhang Xinwen Wang Yin Li Erya Hu Xin Zhou Haicong Liu Qingping Peng Changjing Cai Xiangying Deng Shan Zeng Yihong Chen Zemin Xiao |
| author_sort | Jiayao Ma |
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| description | Abstract Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths globally, owing to its high recurrence rate of 50 to 70% within five years. Despite known associations of certain DNA damage and repair (DDR) genes with tumor recurrence and drug resistance, a comprehensive understanding of DDR pathways’ role in predicting HCC recurrence and therapeutic responses remains elusive. Addressing this gap could offer significant advancements in prognostic and therapeutic strategies for HCC. This study used 769 RNA sequencing samples from public datasets and 53 samples from Xiangya Hospital for DDR model training and validation. It came out that DDR pathways were significantly enriched in samples with P53 mutations. Next, among the 173 combinations of algorithms and parameters, CoxBoost + RSF, Lasso [fold = 10] + RSF, and Lasso [fold = 50] + RSF demonstrated the best performance. The average AUC values of 1 to 5 years and the average concordance index (C-index) value were around 0.7. The risk scores were increased in tumors with recurrence, P53 mutation, and higher TNM stages. High-risk groups, characterized by enriched DDR pathways, exhibited lower CD8 + T cell infiltration and poorer responses to immunotherapy using atezolizumab and bevacizumab, emphasizing the potential of DDR signatures as valuable prognostic and therapeutic biomarkers. In conclusion, the DDR signatures associated with P53 mutations can predict recurrence and therapeutic response in HCC, highlighting their potential as prognostic and therapeutic biomarkers. |
| format | Article |
| id | doaj-art-11d695fbe064488f81d24ca2f39f0b89 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-11d695fbe064488f81d24ca2f39f0b892025-08-20T03:52:23ZengNature PortfolioScientific Reports2045-23222025-04-0115111710.1038/s41598-025-99853-5The molecular characteristics of DNA damage and repair related to P53 mutation for predicting the recurrence and immunotherapy response in hepatocellular carcinomaJiayao Ma0Diya Tang1Guangzu Cui2Xiangyang Zhang3Xinwen Wang4Yin Li5Erya Hu6Xin Zhou7Haicong Liu8Qingping Peng9Changjing Cai10Xiangying Deng11Shan Zeng12Yihong Chen13Zemin Xiao14Department of Oncology, Xiangya Hospital, Central South UniversityDepartment of Oncology, Xiangya Hospital, Central South UniversityDepartment of Oncology, Xiangya Hospital, Central South UniversityDepartment of Oncology, Xiangya Hospital, Central South UniversityDepartment of Oncology, Xiangya Hospital, Central South UniversityDepartment of Oncology, Xiangya Hospital, Central South UniversityDepartment of Oncology, Xiangya Hospital, Central South UniversityDepartment of Oncology, Xiangya Hospital, Central South UniversityDepartment of Oncology, Xiangya Hospital, Central South UniversityDepartment of Oncology, Xiangya Hospital, Central South UniversityDepartment of Oncology, Xiangya Hospital, Central South UniversityDepartment of Oncology, Xiangya Hospital, Central South UniversityDepartment of Oncology, Xiangya Hospital, Central South UniversityDepartment of Oncology, Xiangya Hospital, Central South UniversityDepartment of Oncology, Changde Hospital, Xiangya School of Medicine, Central South University (The first people’s hospital of Changde city)Abstract Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths globally, owing to its high recurrence rate of 50 to 70% within five years. Despite known associations of certain DNA damage and repair (DDR) genes with tumor recurrence and drug resistance, a comprehensive understanding of DDR pathways’ role in predicting HCC recurrence and therapeutic responses remains elusive. Addressing this gap could offer significant advancements in prognostic and therapeutic strategies for HCC. This study used 769 RNA sequencing samples from public datasets and 53 samples from Xiangya Hospital for DDR model training and validation. It came out that DDR pathways were significantly enriched in samples with P53 mutations. Next, among the 173 combinations of algorithms and parameters, CoxBoost + RSF, Lasso [fold = 10] + RSF, and Lasso [fold = 50] + RSF demonstrated the best performance. The average AUC values of 1 to 5 years and the average concordance index (C-index) value were around 0.7. The risk scores were increased in tumors with recurrence, P53 mutation, and higher TNM stages. High-risk groups, characterized by enriched DDR pathways, exhibited lower CD8 + T cell infiltration and poorer responses to immunotherapy using atezolizumab and bevacizumab, emphasizing the potential of DDR signatures as valuable prognostic and therapeutic biomarkers. In conclusion, the DDR signatures associated with P53 mutations can predict recurrence and therapeutic response in HCC, highlighting their potential as prognostic and therapeutic biomarkers.https://doi.org/10.1038/s41598-025-99853-5P53 mutationDNA damage and repairHCC recurrencePrognostic modelImmunotherapy |
| spellingShingle | Jiayao Ma Diya Tang Guangzu Cui Xiangyang Zhang Xinwen Wang Yin Li Erya Hu Xin Zhou Haicong Liu Qingping Peng Changjing Cai Xiangying Deng Shan Zeng Yihong Chen Zemin Xiao The molecular characteristics of DNA damage and repair related to P53 mutation for predicting the recurrence and immunotherapy response in hepatocellular carcinoma Scientific Reports P53 mutation DNA damage and repair HCC recurrence Prognostic model Immunotherapy |
| title | The molecular characteristics of DNA damage and repair related to P53 mutation for predicting the recurrence and immunotherapy response in hepatocellular carcinoma |
| title_full | The molecular characteristics of DNA damage and repair related to P53 mutation for predicting the recurrence and immunotherapy response in hepatocellular carcinoma |
| title_fullStr | The molecular characteristics of DNA damage and repair related to P53 mutation for predicting the recurrence and immunotherapy response in hepatocellular carcinoma |
| title_full_unstemmed | The molecular characteristics of DNA damage and repair related to P53 mutation for predicting the recurrence and immunotherapy response in hepatocellular carcinoma |
| title_short | The molecular characteristics of DNA damage and repair related to P53 mutation for predicting the recurrence and immunotherapy response in hepatocellular carcinoma |
| title_sort | molecular characteristics of dna damage and repair related to p53 mutation for predicting the recurrence and immunotherapy response in hepatocellular carcinoma |
| topic | P53 mutation DNA damage and repair HCC recurrence Prognostic model Immunotherapy |
| url | https://doi.org/10.1038/s41598-025-99853-5 |
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