Enhancing prognostic power in multiple myeloma using a plasma cell signature derived from single-cell RNA sequencing
Abstract Multiple myeloma (MM) is a heterogenous plasma cell malignancy, for which the established prognostic models exhibit limitations in capturing the full spectrum of outcome variability. Leveraging single-cell RNA-sequencing data, we developed a novel plasma cell gene signature. We evaluated an...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2024-03-01
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| Series: | Blood Cancer Journal |
| Online Access: | https://doi.org/10.1038/s41408-024-01024-8 |
| _version_ | 1797266915484237824 |
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| author | Jian-rong Li Shahram Arsang-Jang Yan Cheng Fumou Sun Anita D’Souza Binod Dhakal Parameswaran Hari Quillan Huang Paul Auer Yong Li Raul Urrutia Fenghuang Zhan John D. Shaughnessy Siegfried Janz Jing Dong Chao Cheng |
| author_facet | Jian-rong Li Shahram Arsang-Jang Yan Cheng Fumou Sun Anita D’Souza Binod Dhakal Parameswaran Hari Quillan Huang Paul Auer Yong Li Raul Urrutia Fenghuang Zhan John D. Shaughnessy Siegfried Janz Jing Dong Chao Cheng |
| author_sort | Jian-rong Li |
| collection | DOAJ |
| description | Abstract Multiple myeloma (MM) is a heterogenous plasma cell malignancy, for which the established prognostic models exhibit limitations in capturing the full spectrum of outcome variability. Leveraging single-cell RNA-sequencing data, we developed a novel plasma cell gene signature. We evaluated and validated the associations of the resulting plasma cell malignancy (PBM) score with disease state, progression and clinical outcomes using data from five independent myeloma studies consisting of 2115 samples (1978 MM, 65 monoclonal gammopathy of undetermined significance, 35 smoldering MM, and 37 healthy controls). Overall, a higher PBM score was significantly associated with a more advanced stage within the spectrum of plasma cell dyscrasias (all p < 0.05) and a shorter overall survival in MM (hazard ratio, HR = 1.72; p < 0.001). Notably, the prognostic effect of the PBM score was independent of the International Staging System (ISS) and Revised ISS (R-ISS). The downstream analysis further linked higher PBM scores with the presence of cytogenetic abnormalities, TP53 mutations, and compositional changes in the myeloma tumor immune microenvironment. Our integrated analyses suggest the PBM score may provide an opportunity for refining risk stratification and guide decisions on therapeutic approaches to MM. |
| first_indexed | 2024-04-25T01:08:17Z |
| format | Article |
| id | doaj.art-82447a8befb941718ae624e1ab75d3e4 |
| institution | Directory Open Access Journal |
| issn | 2044-5385 |
| language | English |
| last_indexed | 2024-04-25T01:08:17Z |
| publishDate | 2024-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Blood Cancer Journal |
| spelling | doaj.art-82447a8befb941718ae624e1ab75d3e42024-03-10T12:06:17ZengNature Publishing GroupBlood Cancer Journal2044-53852024-03-011411910.1038/s41408-024-01024-8Enhancing prognostic power in multiple myeloma using a plasma cell signature derived from single-cell RNA sequencingJian-rong Li0Shahram Arsang-Jang1Yan Cheng2Fumou Sun3Anita D’Souza4Binod Dhakal5Parameswaran Hari6Quillan Huang7Paul Auer8Yong Li9Raul Urrutia10Fenghuang Zhan11John D. Shaughnessy12Siegfried Janz13Jing Dong14Chao Cheng15Department of Medicine, Baylor College of MedicineDivision of Hematology Oncology, Department of Medicine, Medical College of WisconsinMyeloma Center, Winthrop P. Rockefeller Cancer Institute, Department of Internal Medicine, University of Arkansas for Medical SciencesMyeloma Center, Winthrop P. Rockefeller Cancer Institute, Department of Internal Medicine, University of Arkansas for Medical SciencesDivision of Hematology Oncology, Department of Medicine, Medical College of WisconsinDivision of Hematology Oncology, Department of Medicine, Medical College of WisconsinDivision of Hematology Oncology, Department of Medicine, Medical College of WisconsinDepartment of Hematology/Oncology, Baylor College of MedicineDivision of Biostatistics, Institute for Health & Equity, and Cancer Center, Medical College of WisconsinDepartment of Medicine, Baylor College of MedicineLinda T. and John A. Mellowes Center for Genomic Sciences and Precision Medicine, Medical College of WisconsinMyeloma Center, Winthrop P. Rockefeller Cancer Institute, Department of Internal Medicine, University of Arkansas for Medical SciencesMyeloma Center, Winthrop P. Rockefeller Cancer Institute, Department of Internal Medicine, University of Arkansas for Medical SciencesDivision of Hematology Oncology, Department of Medicine, Medical College of WisconsinDivision of Hematology Oncology, Department of Medicine, Medical College of WisconsinDepartment of Medicine, Baylor College of MedicineAbstract Multiple myeloma (MM) is a heterogenous plasma cell malignancy, for which the established prognostic models exhibit limitations in capturing the full spectrum of outcome variability. Leveraging single-cell RNA-sequencing data, we developed a novel plasma cell gene signature. We evaluated and validated the associations of the resulting plasma cell malignancy (PBM) score with disease state, progression and clinical outcomes using data from five independent myeloma studies consisting of 2115 samples (1978 MM, 65 monoclonal gammopathy of undetermined significance, 35 smoldering MM, and 37 healthy controls). Overall, a higher PBM score was significantly associated with a more advanced stage within the spectrum of plasma cell dyscrasias (all p < 0.05) and a shorter overall survival in MM (hazard ratio, HR = 1.72; p < 0.001). Notably, the prognostic effect of the PBM score was independent of the International Staging System (ISS) and Revised ISS (R-ISS). The downstream analysis further linked higher PBM scores with the presence of cytogenetic abnormalities, TP53 mutations, and compositional changes in the myeloma tumor immune microenvironment. Our integrated analyses suggest the PBM score may provide an opportunity for refining risk stratification and guide decisions on therapeutic approaches to MM.https://doi.org/10.1038/s41408-024-01024-8 |
| spellingShingle | Jian-rong Li Shahram Arsang-Jang Yan Cheng Fumou Sun Anita D’Souza Binod Dhakal Parameswaran Hari Quillan Huang Paul Auer Yong Li Raul Urrutia Fenghuang Zhan John D. Shaughnessy Siegfried Janz Jing Dong Chao Cheng Enhancing prognostic power in multiple myeloma using a plasma cell signature derived from single-cell RNA sequencing Blood Cancer Journal |
| title | Enhancing prognostic power in multiple myeloma using a plasma cell signature derived from single-cell RNA sequencing |
| title_full | Enhancing prognostic power in multiple myeloma using a plasma cell signature derived from single-cell RNA sequencing |
| title_fullStr | Enhancing prognostic power in multiple myeloma using a plasma cell signature derived from single-cell RNA sequencing |
| title_full_unstemmed | Enhancing prognostic power in multiple myeloma using a plasma cell signature derived from single-cell RNA sequencing |
| title_short | Enhancing prognostic power in multiple myeloma using a plasma cell signature derived from single-cell RNA sequencing |
| title_sort | enhancing prognostic power in multiple myeloma using a plasma cell signature derived from single cell rna sequencing |
| url | https://doi.org/10.1038/s41408-024-01024-8 |
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