Integrated bulk and single-cell RNA sequencing reveals a cuproptosis-related LncRNA prognostic signature in neuroblastoma
Abstract Background Neuroblastoma (NB), the most common extracranial solid tumor of childhood, originates from developing sympathetic nervous system. While cuproptosis has emerged as a critical regulator in oncobiology, its mechanistic involvement in NB remains poorly characterized. Methods RNA-seq...
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2025-07-01
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| Online Access: | https://doi.org/10.1186/s12885-025-14463-8 |
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| author | Ke Chen Jing Wang Shimin Yang Jun Xiao Luyao Wu Zejian Li Xiang Zhao Xuyong Chen Honglin Li Jiexiong Feng Xinyao Meng |
| author_facet | Ke Chen Jing Wang Shimin Yang Jun Xiao Luyao Wu Zejian Li Xiang Zhao Xuyong Chen Honglin Li Jiexiong Feng Xinyao Meng |
| author_sort | Ke Chen |
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| description | Abstract Background Neuroblastoma (NB), the most common extracranial solid tumor of childhood, originates from developing sympathetic nervous system. While cuproptosis has emerged as a critical regulator in oncobiology, its mechanistic involvement in NB remains poorly characterized. Methods RNA-seq data of NB patients was analyzed using limma and ClusterProfiler. CRlncRNAs were identified through Pearson correlation between lncRNAs and CRGs, with co-expression networks visualized via ggalluvial. Prognostic signature was constructed through Lasso-penetrated Cox regression and validated via EFS analysis, C-index, and ROC curves. Somatic mutations and TMB were profiled using maftools. Immune infiltration landscapes were deciphered by CIBERSORT, while single-cell analysis integrated AddModuleScore, AUCell, and inferCNV to map CNV-driven transcriptional heterogeneity. Functional validation via siRNA knockdown confirmed the oncogenic role of CRGs. Results The risk model: Risk Score = (-1.637×DIRC3-AS1) + (0.6758×FOXN3-AS1) + (0.3032×LINC00682) + (-0.6812×RASSF8-AS1) was constructed. Stratification by median risk score revealed significantly prolonged EFS and OS. No significant TMB difference was observed between subgroups. scRNA-seq analysis highlighted malignant cell dominance with marked CNVs in high-risk patients. Functional validation confirmed CRlncRNAs’ roles in modulating proliferation and migration. Conclusion Our findings establish a novel prognostic framework for NB that enhances risk stratification accuracy and provides actionable biomarkers to guide precision clinical management. |
| format | Article |
| id | doaj-art-dd15ab2776b746048791a89425d0c2d6 |
| institution | Kabale University |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj-art-dd15ab2776b746048791a89425d0c2d62025-08-20T04:01:34ZengBMCBMC Cancer1471-24072025-07-0125111310.1186/s12885-025-14463-8Integrated bulk and single-cell RNA sequencing reveals a cuproptosis-related LncRNA prognostic signature in neuroblastomaKe Chen0Jing Wang1Shimin Yang2Jun Xiao3Luyao Wu4Zejian Li5Xiang Zhao6Xuyong Chen7Honglin Li8Jiexiong Feng9Xinyao Meng10Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and TechnologyDepartment of Pediatric Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and TechnologyDepartment of Pediatric Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and TechnologyDepartment of Pediatric Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and TechnologyDepartment of Pediatric Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and TechnologyDepartment of Pediatric Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and TechnologyDepartment of Pediatric Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and TechnologyDepartment of Pediatric Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and TechnologyDepartment of Nursing, Tongji Hospital, Tongji Medical College of Huazhong University of Science and TechnologyDepartment of Pediatric Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and TechnologyDepartment of Pediatric Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and TechnologyAbstract Background Neuroblastoma (NB), the most common extracranial solid tumor of childhood, originates from developing sympathetic nervous system. While cuproptosis has emerged as a critical regulator in oncobiology, its mechanistic involvement in NB remains poorly characterized. Methods RNA-seq data of NB patients was analyzed using limma and ClusterProfiler. CRlncRNAs were identified through Pearson correlation between lncRNAs and CRGs, with co-expression networks visualized via ggalluvial. Prognostic signature was constructed through Lasso-penetrated Cox regression and validated via EFS analysis, C-index, and ROC curves. Somatic mutations and TMB were profiled using maftools. Immune infiltration landscapes were deciphered by CIBERSORT, while single-cell analysis integrated AddModuleScore, AUCell, and inferCNV to map CNV-driven transcriptional heterogeneity. Functional validation via siRNA knockdown confirmed the oncogenic role of CRGs. Results The risk model: Risk Score = (-1.637×DIRC3-AS1) + (0.6758×FOXN3-AS1) + (0.3032×LINC00682) + (-0.6812×RASSF8-AS1) was constructed. Stratification by median risk score revealed significantly prolonged EFS and OS. No significant TMB difference was observed between subgroups. scRNA-seq analysis highlighted malignant cell dominance with marked CNVs in high-risk patients. Functional validation confirmed CRlncRNAs’ roles in modulating proliferation and migration. Conclusion Our findings establish a novel prognostic framework for NB that enhances risk stratification accuracy and provides actionable biomarkers to guide precision clinical management.https://doi.org/10.1186/s12885-025-14463-8CuproptosisImmune infiltrationLncRNAPrognostic panelNeuroblastomaTMB |
| spellingShingle | Ke Chen Jing Wang Shimin Yang Jun Xiao Luyao Wu Zejian Li Xiang Zhao Xuyong Chen Honglin Li Jiexiong Feng Xinyao Meng Integrated bulk and single-cell RNA sequencing reveals a cuproptosis-related LncRNA prognostic signature in neuroblastoma BMC Cancer Cuproptosis Immune infiltration LncRNA Prognostic panel Neuroblastoma TMB |
| title | Integrated bulk and single-cell RNA sequencing reveals a cuproptosis-related LncRNA prognostic signature in neuroblastoma |
| title_full | Integrated bulk and single-cell RNA sequencing reveals a cuproptosis-related LncRNA prognostic signature in neuroblastoma |
| title_fullStr | Integrated bulk and single-cell RNA sequencing reveals a cuproptosis-related LncRNA prognostic signature in neuroblastoma |
| title_full_unstemmed | Integrated bulk and single-cell RNA sequencing reveals a cuproptosis-related LncRNA prognostic signature in neuroblastoma |
| title_short | Integrated bulk and single-cell RNA sequencing reveals a cuproptosis-related LncRNA prognostic signature in neuroblastoma |
| title_sort | integrated bulk and single cell rna sequencing reveals a cuproptosis related lncrna prognostic signature in neuroblastoma |
| topic | Cuproptosis Immune infiltration LncRNA Prognostic panel Neuroblastoma TMB |
| url | https://doi.org/10.1186/s12885-025-14463-8 |
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