Exosomal miR-200c and miR-141 as cerebrospinal fluid biopsy biomarkers for the response to chemotherapy in primary central nervous system lymphoma

Abstract Background To improve early diagnosis and chemotherapy efficacy monitoring in primary central nervous system lymphoma (PCNSL), cerebrospinal fluid (CSF) exosomal microRNA (miRNA) studies were performed. Method Small RNA sequencing was performed to identify candidate exosomal miRNAs as CSF b...

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Main Authors: Yao Hu, Qingyun Zhang, Zhiyuan Wu, Kun Chen, Xiao Xu, Weizhe Ma, Bobin Chen, Limin Jin, Ming Guan
Format: Article
Language:English
Published: Springer 2023-11-01
Series:Discover Oncology
Subjects:
Online Access:https://doi.org/10.1007/s12672-023-00812-1
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author Yao Hu
Qingyun Zhang
Zhiyuan Wu
Kun Chen
Xiao Xu
Weizhe Ma
Bobin Chen
Limin Jin
Ming Guan
author_facet Yao Hu
Qingyun Zhang
Zhiyuan Wu
Kun Chen
Xiao Xu
Weizhe Ma
Bobin Chen
Limin Jin
Ming Guan
author_sort Yao Hu
collection DOAJ
description Abstract Background To improve early diagnosis and chemotherapy efficacy monitoring in primary central nervous system lymphoma (PCNSL), cerebrospinal fluid (CSF) exosomal microRNA (miRNA) studies were performed. Method Small RNA sequencing was performed to identify candidate exosomal miRNAs as CSF biopsy biomarkers from two patients with de novo PCNSL and two patients in remission after chemotherapy. miR-200c and miR-141 expression in CSF exosomes was further validated using relative quantitative real-time polymerase chain reaction in patients with PCNSL (n = 20), patients with other neurological diseases (n = 10), and normal subjects (n = 10). Receiver operating characteristic (ROC) curve analyses of miR-200c and miR-141 in the diagnosis and prediction of chemotherapy efficacy in PCNSL were performed in patients treated with methotrexate. Additionally, bioinformatics tools were utilized to predict the potential targets of miR-200c and miR-141. Results Exosomal miR-200c and miR-141 levels in CSF from patients with PCNSL were significantly lower than those in control subjects. Importantly, miR-200c and miR-141 were upregulated in patients with PCNSL after chemotherapy (P = 0.002). There was a significant correlation between the levels of miR-141 and IL-10 in CSF (P = 0.04). The combination of miR-200c and miR-141 yielded an area under the ROC curve of 0.761 for distinguishing PCNSL with sensitivity and specificity of 60.0% and 96.7%, respectively. The potential target genes of miR-200c and miR-141 in PCNSL included ATP1B3, DYNC1H1, MATR3, NUCKS1, ZNF638, NUDT4, RCN2, GNPDA1, ZBTB38, and DOLK. Conclusion Collectively, miR-200c and miR-141 are likely to be upregulated in CSF exosomes after chemotherapy in patients with PCNSL, highlighting their potential as reliable liquid biopsy biomarkers for PCNSL diagnosis and chemotherapy efficacy monitoring.
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spelling doaj.art-bdbe29ccdf334b309e4f87d01d11a5b62023-11-20T09:50:26ZengSpringerDiscover Oncology2730-60112023-11-0114111210.1007/s12672-023-00812-1Exosomal miR-200c and miR-141 as cerebrospinal fluid biopsy biomarkers for the response to chemotherapy in primary central nervous system lymphomaYao Hu0Qingyun Zhang1Zhiyuan Wu2Kun Chen3Xiao Xu4Weizhe Ma5Bobin Chen6Limin Jin7Ming Guan8Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan UniversityDepartment of Central Laboratory, Huashan Hospital, Shanghai Medical College, Fudan UniversityDepartment of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan UniversityDepartment of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan UniversityDepartment of Central Laboratory, Huashan Hospital, Shanghai Medical College, Fudan UniversityDepartment of Central Laboratory, Huashan Hospital, Shanghai Medical College, Fudan UniversityDepartment of Hematology, Huashan Hospital, Shanghai Medical College, Fudan UniversityDepartment of Laboratory Medicine, Jiaxing Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical UniversityDepartment of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan UniversityAbstract Background To improve early diagnosis and chemotherapy efficacy monitoring in primary central nervous system lymphoma (PCNSL), cerebrospinal fluid (CSF) exosomal microRNA (miRNA) studies were performed. Method Small RNA sequencing was performed to identify candidate exosomal miRNAs as CSF biopsy biomarkers from two patients with de novo PCNSL and two patients in remission after chemotherapy. miR-200c and miR-141 expression in CSF exosomes was further validated using relative quantitative real-time polymerase chain reaction in patients with PCNSL (n = 20), patients with other neurological diseases (n = 10), and normal subjects (n = 10). Receiver operating characteristic (ROC) curve analyses of miR-200c and miR-141 in the diagnosis and prediction of chemotherapy efficacy in PCNSL were performed in patients treated with methotrexate. Additionally, bioinformatics tools were utilized to predict the potential targets of miR-200c and miR-141. Results Exosomal miR-200c and miR-141 levels in CSF from patients with PCNSL were significantly lower than those in control subjects. Importantly, miR-200c and miR-141 were upregulated in patients with PCNSL after chemotherapy (P = 0.002). There was a significant correlation between the levels of miR-141 and IL-10 in CSF (P = 0.04). The combination of miR-200c and miR-141 yielded an area under the ROC curve of 0.761 for distinguishing PCNSL with sensitivity and specificity of 60.0% and 96.7%, respectively. The potential target genes of miR-200c and miR-141 in PCNSL included ATP1B3, DYNC1H1, MATR3, NUCKS1, ZNF638, NUDT4, RCN2, GNPDA1, ZBTB38, and DOLK. Conclusion Collectively, miR-200c and miR-141 are likely to be upregulated in CSF exosomes after chemotherapy in patients with PCNSL, highlighting their potential as reliable liquid biopsy biomarkers for PCNSL diagnosis and chemotherapy efficacy monitoring.https://doi.org/10.1007/s12672-023-00812-1Primary central nervous system lymphomaCerebrospinal fluidExosomemicroRNAChemotherapy
spellingShingle Yao Hu
Qingyun Zhang
Zhiyuan Wu
Kun Chen
Xiao Xu
Weizhe Ma
Bobin Chen
Limin Jin
Ming Guan
Exosomal miR-200c and miR-141 as cerebrospinal fluid biopsy biomarkers for the response to chemotherapy in primary central nervous system lymphoma
Discover Oncology
Primary central nervous system lymphoma
Cerebrospinal fluid
Exosome
microRNA
Chemotherapy
title Exosomal miR-200c and miR-141 as cerebrospinal fluid biopsy biomarkers for the response to chemotherapy in primary central nervous system lymphoma
title_full Exosomal miR-200c and miR-141 as cerebrospinal fluid biopsy biomarkers for the response to chemotherapy in primary central nervous system lymphoma
title_fullStr Exosomal miR-200c and miR-141 as cerebrospinal fluid biopsy biomarkers for the response to chemotherapy in primary central nervous system lymphoma
title_full_unstemmed Exosomal miR-200c and miR-141 as cerebrospinal fluid biopsy biomarkers for the response to chemotherapy in primary central nervous system lymphoma
title_short Exosomal miR-200c and miR-141 as cerebrospinal fluid biopsy biomarkers for the response to chemotherapy in primary central nervous system lymphoma
title_sort exosomal mir 200c and mir 141 as cerebrospinal fluid biopsy biomarkers for the response to chemotherapy in primary central nervous system lymphoma
topic Primary central nervous system lymphoma
Cerebrospinal fluid
Exosome
microRNA
Chemotherapy
url https://doi.org/10.1007/s12672-023-00812-1
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