Genomic and molecular landscape of homologous recombination deficiency across multiple cancer types
Abstract Homologous recombination deficiency (HRD) causes faulty double-strand break repair and is a prevalent cause of tumorigenesis. However, the incidence of HRD and its clinical significance in pan-cancer patients remain unknown. Using computational analysis of Single-nucleotide polymorphism arr...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-35092-w |
| _version_ | 1797811527941619712 |
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| author | Zhiwen Shi Bolin Chen Xiao Han Weiyue Gu Shuzhi Liang Lin Wu |
| author_facet | Zhiwen Shi Bolin Chen Xiao Han Weiyue Gu Shuzhi Liang Lin Wu |
| author_sort | Zhiwen Shi |
| collection | DOAJ |
| description | Abstract Homologous recombination deficiency (HRD) causes faulty double-strand break repair and is a prevalent cause of tumorigenesis. However, the incidence of HRD and its clinical significance in pan-cancer patients remain unknown. Using computational analysis of Single-nucleotide polymorphism array data from 10,619 cancer patients, we demonstrate that HRD frequently occurs across multiple cancer types. Analysis of the pan-cancer cohort revealed that HRD is not only a biomarker for ovarian cancer and triple-negative breast cancer, but also has clinical prognostic value in numerous cancer types, including adrenocortical cancer and thymoma. We discovered that homologous recombination–related genes have a high mutation or deletion frequency. Pathway analysis shows HRD is positively correlated with the DNA damage response and the immune-related signaling pathways. Single cell RNA sequencing of tumor-infiltrating lymphocytes reveals a significantly higher proportion of exhausted T cells in HRD patients, indicating pre-existing immunity. Finally, HRD could be utilized to predict pan-cancer patients’ responses to Programmed cell death protein 1 immunotherapy. In summary, our work establishes a comprehensive map of HRD in pan-cancer. The findings have significant implications for expanding the scope of Poly ADP-ribose polymerase inhibitor therapy and, possibly, immunotherapy. |
| first_indexed | 2024-03-13T07:24:02Z |
| format | Article |
| id | doaj.art-21983987002a4471824ae723b9dd2761 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-13T07:24:02Z |
| publishDate | 2023-06-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj.art-21983987002a4471824ae723b9dd27612023-06-04T11:27:30ZengNature PortfolioScientific Reports2045-23222023-06-0113111510.1038/s41598-023-35092-wGenomic and molecular landscape of homologous recombination deficiency across multiple cancer typesZhiwen Shi0Bolin Chen1Xiao Han2Weiyue Gu3Shuzhi Liang4Lin Wu5Department of Translational Medicine Center, Chigene (Beijing) Translational Medical Research Center Co.Department of Thoracic Medical Oncology，Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South UniversityObstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation, Shanghai Institute of Planned Parenthood Research, State Key Laboratory of Genetic Engineering at School of Life Sciences, Institute of Reproduction and Development, Fudan UniversityDepartment of Translational Medicine Center, Chigene (Beijing) Translational Medical Research Center Co.Department of Thoracic Medical Oncology，Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South UniversityDepartment of Thoracic Medical Oncology，Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South UniversityAbstract Homologous recombination deficiency (HRD) causes faulty double-strand break repair and is a prevalent cause of tumorigenesis. However, the incidence of HRD and its clinical significance in pan-cancer patients remain unknown. Using computational analysis of Single-nucleotide polymorphism array data from 10,619 cancer patients, we demonstrate that HRD frequently occurs across multiple cancer types. Analysis of the pan-cancer cohort revealed that HRD is not only a biomarker for ovarian cancer and triple-negative breast cancer, but also has clinical prognostic value in numerous cancer types, including adrenocortical cancer and thymoma. We discovered that homologous recombination–related genes have a high mutation or deletion frequency. Pathway analysis shows HRD is positively correlated with the DNA damage response and the immune-related signaling pathways. Single cell RNA sequencing of tumor-infiltrating lymphocytes reveals a significantly higher proportion of exhausted T cells in HRD patients, indicating pre-existing immunity. Finally, HRD could be utilized to predict pan-cancer patients’ responses to Programmed cell death protein 1 immunotherapy. In summary, our work establishes a comprehensive map of HRD in pan-cancer. The findings have significant implications for expanding the scope of Poly ADP-ribose polymerase inhibitor therapy and, possibly, immunotherapy.https://doi.org/10.1038/s41598-023-35092-w |
| spellingShingle | Zhiwen Shi Bolin Chen Xiao Han Weiyue Gu Shuzhi Liang Lin Wu Genomic and molecular landscape of homologous recombination deficiency across multiple cancer types Scientific Reports |
| title | Genomic and molecular landscape of homologous recombination deficiency across multiple cancer types |
| title_full | Genomic and molecular landscape of homologous recombination deficiency across multiple cancer types |
| title_fullStr | Genomic and molecular landscape of homologous recombination deficiency across multiple cancer types |
| title_full_unstemmed | Genomic and molecular landscape of homologous recombination deficiency across multiple cancer types |
| title_short | Genomic and molecular landscape of homologous recombination deficiency across multiple cancer types |
| title_sort | genomic and molecular landscape of homologous recombination deficiency across multiple cancer types |
| url | https://doi.org/10.1038/s41598-023-35092-w |
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