Decoding the metastatic potential and optimal postoperative adjuvant therapy of melanoma based on metastasis score
Abstract Metastasis is a formidable challenge in the prognosis of melanoma. Accurately predicting the metastatic potential of non-metastatic melanoma (NMM) and determining effective postoperative adjuvant treatments for inhibiting metastasis remain uncertain. In this study, we conducted comprehensiv...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-10-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-023-01678-6 |
| _version_ | 1797453904871424000 |
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| author | Kangjie Shen Wenyu Song Hongye Wang Lu Wang Yang Yang Qianrong Hu Min Ren Zixu Gao Qiangcheng Wang Shaoluan Zheng Ming Zhu Yanwen Yang Yong Zhang Chuanyuan Wei Jianying Gu |
| author_facet | Kangjie Shen Wenyu Song Hongye Wang Lu Wang Yang Yang Qianrong Hu Min Ren Zixu Gao Qiangcheng Wang Shaoluan Zheng Ming Zhu Yanwen Yang Yong Zhang Chuanyuan Wei Jianying Gu |
| author_sort | Kangjie Shen |
| collection | DOAJ |
| description | Abstract Metastasis is a formidable challenge in the prognosis of melanoma. Accurately predicting the metastatic potential of non-metastatic melanoma (NMM) and determining effective postoperative adjuvant treatments for inhibiting metastasis remain uncertain. In this study, we conducted comprehensive analyses of melanoma metastases using bulk and single-cell RNA sequencing data, enabling the construction of a metastasis score (MET score) through diverse machine-learning algorithms. The reliability and robustness of the MET score were validated using various in vitro assays and in vivo models. Our findings revealed a distinct molecular landscape in metastatic melanoma characterized by the enrichment of metastasis-related pathways, intricate cell–cell communication, and heightened infiltration of pro-angiogenic tumor-associated macrophages compared to NMM. Importantly, patients in the high MET score group exhibited poorer prognoses and an immunosuppressive microenvironment, featuring increased infiltration of regulatory T cells and decreased infiltration of CD8+ T cells, compared to the low MET score patient group. Expression of PD-1 was markedly higher in patients with low MET scores. Anti-PD-1 (aPD-1) therapy profoundly affected antitumor immunity activation and metastasis inhibition in these patients. In summary, our study demonstrates the effectiveness of the MET score in predicting melanoma metastatic potential. For patients with low MET scores, aPD-1 therapy may be a potential treatment strategy to inhibit metastasis. Patients with high MET scores may benefit from combination therapies. |
| first_indexed | 2024-03-09T15:29:36Z |
| format | Article |
| id | doaj.art-c8d5e95afefb4072ae5616eadb823832 |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-03-09T15:29:36Z |
| publishDate | 2023-10-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-c8d5e95afefb4072ae5616eadb8238322023-11-26T12:21:20ZengNature Publishing GroupCell Death Discovery2058-77162023-10-019111410.1038/s41420-023-01678-6Decoding the metastatic potential and optimal postoperative adjuvant therapy of melanoma based on metastasis scoreKangjie Shen0Wenyu Song1Hongye Wang2Lu Wang3Yang Yang4Qianrong Hu5Min Ren6Zixu Gao7Qiangcheng Wang8Shaoluan Zheng9Ming Zhu10Yanwen Yang11Yong Zhang12Chuanyuan Wei13Jianying Gu14Department of Plastic Surgery, Zhongshan Hospital, Fudan UniversityDepartment of Cardiovascular Surgery, Zhongshan Hospital, Fudan UniversityDepartment of Interventional Oncology, Renji Hospital, School of Medicine, Shanghai Jiaotong UniversityDepartment of Plastic Surgery, Zhongshan Hospital, Fudan UniversityDepartment of Plastic Surgery, Zhongshan Hospital, Fudan UniversityDepartment of Plastic Surgery, Zhongshan Hospital, Fudan UniversityDepartment of Plastic Surgery, Zhongshan Hospital, Fudan UniversityDepartment of Plastic Surgery, Zhongshan Hospital, Fudan UniversityThe Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer ResearchDepartment of Plastic Surgery, Zhongshan Hospital, Fudan UniversityDepartment of Plastic Surgery, Zhongshan Hospital, Fudan UniversityDepartment of Plastic Surgery, Zhongshan Hospital, Fudan UniversityDepartment of Plastic Surgery, Zhongshan Hospital, Fudan UniversityDepartment of Plastic Surgery, Zhongshan Hospital, Fudan UniversityDepartment of Plastic Surgery, Zhongshan Hospital, Fudan UniversityAbstract Metastasis is a formidable challenge in the prognosis of melanoma. Accurately predicting the metastatic potential of non-metastatic melanoma (NMM) and determining effective postoperative adjuvant treatments for inhibiting metastasis remain uncertain. In this study, we conducted comprehensive analyses of melanoma metastases using bulk and single-cell RNA sequencing data, enabling the construction of a metastasis score (MET score) through diverse machine-learning algorithms. The reliability and robustness of the MET score were validated using various in vitro assays and in vivo models. Our findings revealed a distinct molecular landscape in metastatic melanoma characterized by the enrichment of metastasis-related pathways, intricate cell–cell communication, and heightened infiltration of pro-angiogenic tumor-associated macrophages compared to NMM. Importantly, patients in the high MET score group exhibited poorer prognoses and an immunosuppressive microenvironment, featuring increased infiltration of regulatory T cells and decreased infiltration of CD8+ T cells, compared to the low MET score patient group. Expression of PD-1 was markedly higher in patients with low MET scores. Anti-PD-1 (aPD-1) therapy profoundly affected antitumor immunity activation and metastasis inhibition in these patients. In summary, our study demonstrates the effectiveness of the MET score in predicting melanoma metastatic potential. For patients with low MET scores, aPD-1 therapy may be a potential treatment strategy to inhibit metastasis. Patients with high MET scores may benefit from combination therapies.https://doi.org/10.1038/s41420-023-01678-6 |
| spellingShingle | Kangjie Shen Wenyu Song Hongye Wang Lu Wang Yang Yang Qianrong Hu Min Ren Zixu Gao Qiangcheng Wang Shaoluan Zheng Ming Zhu Yanwen Yang Yong Zhang Chuanyuan Wei Jianying Gu Decoding the metastatic potential and optimal postoperative adjuvant therapy of melanoma based on metastasis score Cell Death Discovery |
| title | Decoding the metastatic potential and optimal postoperative adjuvant therapy of melanoma based on metastasis score |
| title_full | Decoding the metastatic potential and optimal postoperative adjuvant therapy of melanoma based on metastasis score |
| title_fullStr | Decoding the metastatic potential and optimal postoperative adjuvant therapy of melanoma based on metastasis score |
| title_full_unstemmed | Decoding the metastatic potential and optimal postoperative adjuvant therapy of melanoma based on metastasis score |
| title_short | Decoding the metastatic potential and optimal postoperative adjuvant therapy of melanoma based on metastasis score |
| title_sort | decoding the metastatic potential and optimal postoperative adjuvant therapy of melanoma based on metastasis score |
| url | https://doi.org/10.1038/s41420-023-01678-6 |
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