Integrating single-cell and bulk RNA profiles to uncover glutamine metabolism’s role in prognosis and immune dynamics in multiple myeloma
Abstract Objective Multiple myeloma (MM) exhibits significant heterogeneity, leading to variable treatment responses and poor clinical outcomes. Glutamine metabolism-related genes (GMRGs) represent critical regulators of tumor biology, yet their prognostic and therapeutic significance in MM remains...
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2025-05-01
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| Online Access: | https://doi.org/10.1186/s12885-025-14239-0 |
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| author | Fei Zhao Feifei Che |
| author_facet | Fei Zhao Feifei Che |
| author_sort | Fei Zhao |
| collection | DOAJ |
| description | Abstract Objective Multiple myeloma (MM) exhibits significant heterogeneity, leading to variable treatment responses and poor clinical outcomes. Glutamine metabolism-related genes (GMRGs) represent critical regulators of tumor biology, yet their prognostic and therapeutic significance in MM remains unexplored. This study aims to identify GMRG-driven tumor signatures and establish their clinical utility as prognostic biomarkers, therapeutic targets and enhancers of drug sensitivity. Methods Integrated transcriptomic and single-cell sequencing analyses of public multi-omics cohorts enabled systematic identification of GMRGs in MM through weighted co-expression network analysis coupled with univariate Cox proportional hazards modeling. Clinically prioritized GMRGs showing elevated expression in patient specimens were functionally validated through proliferation assays and pharmacological sensitivity profiling. Results Integrated multi-omics analysis combining single-cell sequencing with bulk transcriptomic profiling and prognostic screening identified 51 prognostic GMRGs, with 10 core signature genes selected for model construction. The risk stratification system demonstrated robust prognostic capacity validated across multiple independent MM cohorts. Pathway enrichment revealed significant involvement in immune system, cell cycle and tumor signaling. MM patient validation identified DLD, SFT2D2, and UBA2 as significantly upregulated genes that promote tumor growth through enhancement of proliferation. Mechanistic investigations via shRNA-mediated knockdown established that DLD and UBA2 silencing significantly enhanced therapeutic efficacy of MM inhibitors. Conclusion Multicohort-validated GMRGs (DLD/UBA2) drive MM progression and MM inhibitor responses. Clinical upregulation and functional silencing confirm dual therapeutic potential as prognostic biomarkers and drug-sensitizing targets. |
| format | Article |
| id | doaj-art-1603379b856246a881fc0c3661cee2a5 |
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| issn | 1471-2407 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
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| series | BMC Cancer |
| spelling | doaj-art-1603379b856246a881fc0c3661cee2a52025-08-20T01:53:14ZengBMCBMC Cancer1471-24072025-05-0125111210.1186/s12885-025-14239-0Integrating single-cell and bulk RNA profiles to uncover glutamine metabolism’s role in prognosis and immune dynamics in multiple myelomaFei Zhao0Feifei Che1Institute of HematoFlogy, Union Hospital, Huazhong University of Science and TechnologyDepartment of Hemotology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of ChinaAbstract Objective Multiple myeloma (MM) exhibits significant heterogeneity, leading to variable treatment responses and poor clinical outcomes. Glutamine metabolism-related genes (GMRGs) represent critical regulators of tumor biology, yet their prognostic and therapeutic significance in MM remains unexplored. This study aims to identify GMRG-driven tumor signatures and establish their clinical utility as prognostic biomarkers, therapeutic targets and enhancers of drug sensitivity. Methods Integrated transcriptomic and single-cell sequencing analyses of public multi-omics cohorts enabled systematic identification of GMRGs in MM through weighted co-expression network analysis coupled with univariate Cox proportional hazards modeling. Clinically prioritized GMRGs showing elevated expression in patient specimens were functionally validated through proliferation assays and pharmacological sensitivity profiling. Results Integrated multi-omics analysis combining single-cell sequencing with bulk transcriptomic profiling and prognostic screening identified 51 prognostic GMRGs, with 10 core signature genes selected for model construction. The risk stratification system demonstrated robust prognostic capacity validated across multiple independent MM cohorts. Pathway enrichment revealed significant involvement in immune system, cell cycle and tumor signaling. MM patient validation identified DLD, SFT2D2, and UBA2 as significantly upregulated genes that promote tumor growth through enhancement of proliferation. Mechanistic investigations via shRNA-mediated knockdown established that DLD and UBA2 silencing significantly enhanced therapeutic efficacy of MM inhibitors. Conclusion Multicohort-validated GMRGs (DLD/UBA2) drive MM progression and MM inhibitor responses. Clinical upregulation and functional silencing confirm dual therapeutic potential as prognostic biomarkers and drug-sensitizing targets.https://doi.org/10.1186/s12885-025-14239-0Multiple myelomaGlutamine metabolism-related genes (GMRGs)PrognosisImmune infiltrationBiomarker |
| spellingShingle | Fei Zhao Feifei Che Integrating single-cell and bulk RNA profiles to uncover glutamine metabolism’s role in prognosis and immune dynamics in multiple myeloma BMC Cancer Multiple myeloma Glutamine metabolism-related genes (GMRGs) Prognosis Immune infiltration Biomarker |
| title | Integrating single-cell and bulk RNA profiles to uncover glutamine metabolism’s role in prognosis and immune dynamics in multiple myeloma |
| title_full | Integrating single-cell and bulk RNA profiles to uncover glutamine metabolism’s role in prognosis and immune dynamics in multiple myeloma |
| title_fullStr | Integrating single-cell and bulk RNA profiles to uncover glutamine metabolism’s role in prognosis and immune dynamics in multiple myeloma |
| title_full_unstemmed | Integrating single-cell and bulk RNA profiles to uncover glutamine metabolism’s role in prognosis and immune dynamics in multiple myeloma |
| title_short | Integrating single-cell and bulk RNA profiles to uncover glutamine metabolism’s role in prognosis and immune dynamics in multiple myeloma |
| title_sort | integrating single cell and bulk rna profiles to uncover glutamine metabolism s role in prognosis and immune dynamics in multiple myeloma |
| topic | Multiple myeloma Glutamine metabolism-related genes (GMRGs) Prognosis Immune infiltration Biomarker |
| url | https://doi.org/10.1186/s12885-025-14239-0 |
| work_keys_str_mv | AT feizhao integratingsinglecellandbulkrnaprofilestouncoverglutaminemetabolismsroleinprognosisandimmunedynamicsinmultiplemyeloma AT feifeiche integratingsinglecellandbulkrnaprofilestouncoverglutaminemetabolismsroleinprognosisandimmunedynamicsinmultiplemyeloma |