Proteogenomic analysis dissects early-onset breast cancer patients with prognostic relevance
Abstract Early-onset breast cancer is known for its aggressive clinical characteristics and high prevalence in East Asian countries, but a comprehensive understanding of its molecular features is still lacking. In this study, we conducted a proteogenomic analysis of 126 treatment-naïve primary tumor...
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| Format: | Article |
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Nature Publishing Group
2024-11-01
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| Series: | Experimental and Molecular Medicine |
| Online Access: | https://doi.org/10.1038/s12276-024-01332-w |
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| author | Kyong-Ah Yoon Youngwook Kim So-Youn Jung Jin-Sun Ryu Kyung-Hee Kim Eun-Gyeong Lee Heejung Chae Youngmee Kwon Jaegil Kim Jong Bae Park Sun-Young Kong |
| author_facet | Kyong-Ah Yoon Youngwook Kim So-Youn Jung Jin-Sun Ryu Kyung-Hee Kim Eun-Gyeong Lee Heejung Chae Youngmee Kwon Jaegil Kim Jong Bae Park Sun-Young Kong |
| author_sort | Kyong-Ah Yoon |
| collection | DOAJ |
| description | Abstract Early-onset breast cancer is known for its aggressive clinical characteristics and high prevalence in East Asian countries, but a comprehensive understanding of its molecular features is still lacking. In this study, we conducted a proteogenomic analysis of 126 treatment-naïve primary tumor tissues obtained from Korean patients with young breast cancer (YBC) aged ≤40 years. By integrating genomic, transcriptomic, and proteomic data, we identified five distinct functional subgroups that accurately represented the clinical characteristics and biological behaviors of patients with YBC. Our integrated approach could be used to determine the proteogenomic status of HER2, enhancing its clinical significance and prognostic value. Furthermore, we present a proteome-based homologous recombination deficiency (HRD) analysis that has the potential to overcome the limitations of conventional genomic HRD tests, facilitating the identification of new patient groups requiring targeted HR deficiency treatments. Additionally, we demonstrated that protein–RNA correlations can be used to predict the late recurrence of hormone receptor-positive breast cancer. Within each molecular subtype of breast cancer, we identified functionally significant protein groups whose differential abundance was closely correlated with the clinical progression of breast cancer. Furthermore, we derived a recurrence predictive index capable of predicting late recurrence, specifically in luminal subtypes, which plays a crucial role in guiding decisions on treatment durations for YBC patients. These findings improve the stratification and clinical implications for patients with YBC by contributing to the optimal adjuvant treatment and duration for favorable clinical outcomes. |
| format | Article |
| id | doaj-art-9a4265ecd7984d9bb4bb28f58b6cc038 |
| institution | OA Journals |
| issn | 2092-6413 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Experimental and Molecular Medicine |
| spelling | doaj-art-9a4265ecd7984d9bb4bb28f58b6cc0382025-08-20T02:20:38ZengNature Publishing GroupExperimental and Molecular Medicine2092-64132024-11-0156112382239410.1038/s12276-024-01332-wProteogenomic analysis dissects early-onset breast cancer patients with prognostic relevanceKyong-Ah Yoon0Youngwook Kim1So-Youn Jung2Jin-Sun Ryu3Kyung-Hee Kim4Eun-Gyeong Lee5Heejung Chae6Youngmee Kwon7Jaegil Kim8Jong Bae Park9Sun-Young Kong10Department of Biochemistry, College of Veterinary Medicine, Konkuk UniversityDepartment of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer CenterDepartment of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer CenterDivision of Translational Science, Research Institute, National Cancer CenterDepartment of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer CenterCenter for Breast Cancer, National Cancer CenterCancer Data Center, Control Institute, National Cancer CenterCenter for Breast Cancer, National Cancer CenterGlaxoSmithKlineDepartment of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer CenterDepartment of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer CenterAbstract Early-onset breast cancer is known for its aggressive clinical characteristics and high prevalence in East Asian countries, but a comprehensive understanding of its molecular features is still lacking. In this study, we conducted a proteogenomic analysis of 126 treatment-naïve primary tumor tissues obtained from Korean patients with young breast cancer (YBC) aged ≤40 years. By integrating genomic, transcriptomic, and proteomic data, we identified five distinct functional subgroups that accurately represented the clinical characteristics and biological behaviors of patients with YBC. Our integrated approach could be used to determine the proteogenomic status of HER2, enhancing its clinical significance and prognostic value. Furthermore, we present a proteome-based homologous recombination deficiency (HRD) analysis that has the potential to overcome the limitations of conventional genomic HRD tests, facilitating the identification of new patient groups requiring targeted HR deficiency treatments. Additionally, we demonstrated that protein–RNA correlations can be used to predict the late recurrence of hormone receptor-positive breast cancer. Within each molecular subtype of breast cancer, we identified functionally significant protein groups whose differential abundance was closely correlated with the clinical progression of breast cancer. Furthermore, we derived a recurrence predictive index capable of predicting late recurrence, specifically in luminal subtypes, which plays a crucial role in guiding decisions on treatment durations for YBC patients. These findings improve the stratification and clinical implications for patients with YBC by contributing to the optimal adjuvant treatment and duration for favorable clinical outcomes.https://doi.org/10.1038/s12276-024-01332-w |
| spellingShingle | Kyong-Ah Yoon Youngwook Kim So-Youn Jung Jin-Sun Ryu Kyung-Hee Kim Eun-Gyeong Lee Heejung Chae Youngmee Kwon Jaegil Kim Jong Bae Park Sun-Young Kong Proteogenomic analysis dissects early-onset breast cancer patients with prognostic relevance Experimental and Molecular Medicine |
| title | Proteogenomic analysis dissects early-onset breast cancer patients with prognostic relevance |
| title_full | Proteogenomic analysis dissects early-onset breast cancer patients with prognostic relevance |
| title_fullStr | Proteogenomic analysis dissects early-onset breast cancer patients with prognostic relevance |
| title_full_unstemmed | Proteogenomic analysis dissects early-onset breast cancer patients with prognostic relevance |
| title_short | Proteogenomic analysis dissects early-onset breast cancer patients with prognostic relevance |
| title_sort | proteogenomic analysis dissects early onset breast cancer patients with prognostic relevance |
| url | https://doi.org/10.1038/s12276-024-01332-w |
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