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. 2023 Nov 16;14(1):205.
doi: 10.1007/s12672-023-00812-1.

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

Yao Hu  1 , Qingyun Zhang  2 , Zhiyuan Wu  1 , Kun Chen  1 , Xiao Xu  2 , Weizhe Ma  2 , Bobin Chen  3 , Limin Jin  4 , Ming Guan  5
Affiliations

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

Yao Hu et al. Discov Oncol. .

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.

Keywords: Cerebrospinal fluid; Chemotherapy; Exosome; Primary central nervous system lymphoma; microRNA.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Fig. 1
Fig. 1
A Volcano plot of miR-200c and miR-141 expression in CSF-derived exosomes between patients with de novo PCNSL diagnosis and patients with previously treated PCNSL. B The interaction network diagram of miR-200c and miR-141
Fig. 2
Fig. 2
Comparison of the expression of miR-200c (A) and miR-141 (B) in CSF exosomes in the study population. The relative expression of miR-200c (C) and miR-141 (D) significantly differed between the de novo PCNSL and control groups. The Mann–Whitney U test was used for analysis (*P < 0.001).
Fig. 3
Fig. 3
ROC curve analysis of CSF exosomal miR-200c (A), miR-141 (B), and miR-200c + miR-141 (C) for diagnosing PCNSL
Fig. 4
Fig. 4
Changes of CSF exosomal miR-200c and miR-141 expression following chemotherapy. The relative expression of miR-200c (A) and miR-141 (B) was significantly increased in patients with PCNSL after chemotherapy. The Mann–Whitney U test was used for analysis (*P < 0.001; NS: not significant)
Fig. 5
Fig. 5
ROC curve analyses of miR-200c (A) and miR-141 (B) for predicting the response to MTX treatment in patients with PCNSL
Fig. 6
Fig. 6
Relationships of ATP1B3, DYNC1H1, MATR3, NUCKS1, ZNF638, NUDT4, RCN2, GNPDA1, ZBTB38, and DOLK with survival in DLBCL
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