Diagnostic and prognostic potential of cell-free RNAs in cerebrospinal fluid and plasma for brain tumors

Abstract Systematic assessment of the clinical applicability of cell-free RNAs (cfRNAs), which includes broader RNA categories beyond microRNAs, for patients with brain tumors remains largely unexplored due to the lack of sensitive profiling technologies. Our study endeavors to bridge this gap by ut...

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Main Authors: Jinyong Huang, Jinxia Zhou, Jun Wang, Yonghao Yi, Lu Zhang, Shuyong Qiu, Yuanyan Tan, Qianwen Guo, Feilong Zhao, Xinying Li, Yanqin Niu, Haoyu Li, Changwu Wu, Kang Kang, Qing Liu, Deming Gou
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:npj Precision Oncology
Online Access:https://doi.org/10.1038/s41698-025-00909-6
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author Jinyong Huang
Jinxia Zhou
Jun Wang
Yonghao Yi
Lu Zhang
Shuyong Qiu
Yuanyan Tan
Qianwen Guo
Feilong Zhao
Xinying Li
Yanqin Niu
Haoyu Li
Changwu Wu
Kang Kang
Qing Liu
Deming Gou
author_facet Jinyong Huang
Jinxia Zhou
Jun Wang
Yonghao Yi
Lu Zhang
Shuyong Qiu
Yuanyan Tan
Qianwen Guo
Feilong Zhao
Xinying Li
Yanqin Niu
Haoyu Li
Changwu Wu
Kang Kang
Qing Liu
Deming Gou
author_sort Jinyong Huang
collection DOAJ
description Abstract Systematic assessment of the clinical applicability of cell-free RNAs (cfRNAs), which includes broader RNA categories beyond microRNAs, for patients with brain tumors remains largely unexplored due to the lack of sensitive profiling technologies. Our study endeavors to bridge this gap by utilizing an optimized cell-free transcriptome profiling technique that we have recently developed. We comprehensively profiled the cell-free transcriptome in plasma and cerebrospinal fluid (CSF) samples from a total of 85 patients with glioma, meningioma, or tumor-free central nervous system diseases. We identified 16 cfRNA signatures in CSF with robust performance in brain tumor detection (test set AUC = 0.94; validation set AUC = 1). The integration of CSF and plasma-derived cfRNAs outperformed individual analyses using either CSF or plasma candidates for the classification of glioma (test set AUC = 0.94; validation set AUC = 0.85) and meningioma (test set AUC = 0.92; validation set AUC = 0.83). Additionally, we identified 33 CSF and 3 plasma cfRNAs with prognostic significance for postoperative patient outcomes. Multivariate analysis showed that cfRNA-based risk scores (Hazard ratio=9.9) outperformed traditional risk factors in predicting recurrence-free survival. Importantly, our findings in liquid biopsies are consistent with results from primary tumor tissues. By delving into the diagnostic and prognostic implications of cfRNA signatures in CSF and plasma, our study paves the way for improved diagnostic precision and personalized therapeutic interventions for brain tumor patients.
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spelling doaj-art-c93d5d24fa2f440492c0b0de6d0ad1092025-08-20T03:52:24ZengNature Portfolionpj Precision Oncology2397-768X2025-04-019111210.1038/s41698-025-00909-6Diagnostic and prognostic potential of cell-free RNAs in cerebrospinal fluid and plasma for brain tumorsJinyong Huang0Jinxia Zhou1Jun Wang2Yonghao Yi3Lu Zhang4Shuyong Qiu5Yuanyan Tan6Qianwen Guo7Feilong Zhao8Xinying Li9Yanqin Niu10Haoyu Li11Changwu Wu12Kang Kang13Qing Liu14Deming Gou15Shenzhen Key Laboratory of Microbial Genetic Engineering, Vascular Disease Research Center, College of Life Sciences and Oceanography, Shenzhen University, ShenzhenDepartment of Neurology, Fifth Affiliated Hospital of Sun Yat-Sen UniversityShenzhen Key Laboratory of Microbial Genetic Engineering, Vascular Disease Research Center, College of Life Sciences and Oceanography, Shenzhen University, ShenzhenShenzhen Key Laboratory of Microbial Genetic Engineering, Vascular Disease Research Center, College of Life Sciences and Oceanography, Shenzhen University, ShenzhenShenzhen Key Laboratory of Microbial Genetic Engineering, Vascular Disease Research Center, College of Life Sciences and Oceanography, Shenzhen University, ShenzhenShenzhen Key Laboratory of Microbial Genetic Engineering, Vascular Disease Research Center, College of Life Sciences and Oceanography, Shenzhen University, ShenzhenShenzhen Key Laboratory of Microbial Genetic Engineering, Vascular Disease Research Center, College of Life Sciences and Oceanography, Shenzhen University, ShenzhenShenzhen Key Laboratory of Microbial Genetic Engineering, Vascular Disease Research Center, College of Life Sciences and Oceanography, Shenzhen University, ShenzhenShenzhen Key Laboratory of Microbial Genetic Engineering, Vascular Disease Research Center, College of Life Sciences and Oceanography, Shenzhen University, ShenzhenShenzhen Key Laboratory of Microbial Genetic Engineering, Vascular Disease Research Center, College of Life Sciences and Oceanography, Shenzhen University, ShenzhenShenzhen Key Laboratory of Microbial Genetic Engineering, Vascular Disease Research Center, College of Life Sciences and Oceanography, Shenzhen University, ShenzhenDepartment of Neurosurgery, Xiangya Hospital, Central South UniversityDepartment of Neurosurgery, Xiangya Hospital, Central South UniversityDepartment of Biochemistry and Molecular Biology, Shenzhen University Medical SchoolDepartment of Neurosurgery, Xiangya Hospital, Central South UniversityShenzhen Key Laboratory of Microbial Genetic Engineering, Vascular Disease Research Center, College of Life Sciences and Oceanography, Shenzhen University, ShenzhenAbstract Systematic assessment of the clinical applicability of cell-free RNAs (cfRNAs), which includes broader RNA categories beyond microRNAs, for patients with brain tumors remains largely unexplored due to the lack of sensitive profiling technologies. Our study endeavors to bridge this gap by utilizing an optimized cell-free transcriptome profiling technique that we have recently developed. We comprehensively profiled the cell-free transcriptome in plasma and cerebrospinal fluid (CSF) samples from a total of 85 patients with glioma, meningioma, or tumor-free central nervous system diseases. We identified 16 cfRNA signatures in CSF with robust performance in brain tumor detection (test set AUC = 0.94; validation set AUC = 1). The integration of CSF and plasma-derived cfRNAs outperformed individual analyses using either CSF or plasma candidates for the classification of glioma (test set AUC = 0.94; validation set AUC = 0.85) and meningioma (test set AUC = 0.92; validation set AUC = 0.83). Additionally, we identified 33 CSF and 3 plasma cfRNAs with prognostic significance for postoperative patient outcomes. Multivariate analysis showed that cfRNA-based risk scores (Hazard ratio=9.9) outperformed traditional risk factors in predicting recurrence-free survival. Importantly, our findings in liquid biopsies are consistent with results from primary tumor tissues. By delving into the diagnostic and prognostic implications of cfRNA signatures in CSF and plasma, our study paves the way for improved diagnostic precision and personalized therapeutic interventions for brain tumor patients.https://doi.org/10.1038/s41698-025-00909-6
spellingShingle Jinyong Huang
Jinxia Zhou
Jun Wang
Yonghao Yi
Lu Zhang
Shuyong Qiu
Yuanyan Tan
Qianwen Guo
Feilong Zhao
Xinying Li
Yanqin Niu
Haoyu Li
Changwu Wu
Kang Kang
Qing Liu
Deming Gou
Diagnostic and prognostic potential of cell-free RNAs in cerebrospinal fluid and plasma for brain tumors
npj Precision Oncology
title Diagnostic and prognostic potential of cell-free RNAs in cerebrospinal fluid and plasma for brain tumors
title_full Diagnostic and prognostic potential of cell-free RNAs in cerebrospinal fluid and plasma for brain tumors
title_fullStr Diagnostic and prognostic potential of cell-free RNAs in cerebrospinal fluid and plasma for brain tumors
title_full_unstemmed Diagnostic and prognostic potential of cell-free RNAs in cerebrospinal fluid and plasma for brain tumors
title_short Diagnostic and prognostic potential of cell-free RNAs in cerebrospinal fluid and plasma for brain tumors
title_sort diagnostic and prognostic potential of cell free rnas in cerebrospinal fluid and plasma for brain tumors
url https://doi.org/10.1038/s41698-025-00909-6
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