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Review Special Issue

Advances in cerebrospinal fluid biomarkers for the diagnosis, treatment and monitoring of leptomeningeal metastases (Review)

This article is part of the special Issue: The management of brain metastasis: recent treatment and future directions
  • Authors:
    • Huaixu Li
    • Wenwen Fan
    • Fengchun Mu
    • Cheng Fang
    • Ting Xiao
    • Jinghai Wan
    • Hongqing Cai
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China, Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China, State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
  • Article Number: 266
    |
    Published online on: April 27, 2026
       https://doi.org/10.3892/ol.2026.15621
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Abstract

Leptomeningeal metastasis (LM) is an aggressive complication characterized by the dissemination of malignant cells to the leptomeninges, typically resulting in rapid neurological deterioration and poor prognosis. Clinical diagnosis and management are impeded by non‑specific symptoms and the limited sensitivity of conventional cerebrospinal fluid (CSF) cytology. Consequently, CSF biomarkers have emerged as critical tools for diagnosis, treatment monitoring and prognostic evaluation. The present review summarizes recent advancements in CSF biomarkers, categorizing them into proteins, nucleic acids and metabolites. These biomarkers enhance diagnostic accuracy, facilitate longitudinal disease tracking and assess therapeutic efficacy. Despite notable progress, challenges persist regarding biomarker sensitivity, specificity and standardization. Furthermore, the potential of multi‑omics technologies and single‑cell analysis is discussed as a pathway for discovering novel biomarkers to enable the precise stratification and personalized management of LM.
View Figures

Figure 1

Cerebrospinal fluid biomarkers used
for the diagnosis and treatment of LM. Biomarkers are arranged by
clinical application (diagnosis vs. treatment monitoring) and by
biomarker class (protein, nucleic acid, metabolite and cellular and
other markers), as indicated by the symbols. The central panel
shows a de-identified representative contrast-enhanced brain MRI of
a patient with LM from the National Cancer Center/National Clinical
Research Center for Cancer/Cancer Hospital (Chinese Academy of
Medical Sciences and Peking Union Medical College, Beijing, China).
The white arrows indicate leptomeningeal enhancement. LM,
leptomeningeal metastasis; HE4, human epididymis protein 4;
CEACAM6, carcinoembryonic antigen-related cell adhesion molecule 6;
CEA, carcinoembryonic antigen; PSA, prostate-specific antigen;
CA-125/15-3/19-9, cancer antigen 125/15-3/19-9; MART1, melanoma
antigen recognized by T cells 1; MAGE-3, melanoma-associated
antigen 3; CK7, cytokeratin 7; EpCAM, epithelial cell adhesion
molecule; NfL, neurofilament light chain; LDH, lactate
dehydrogenase; AFP, α-fetoprotein; ABAT, 4-aminobutyrate
aminotransferase; IL-6, interleukin-6; TNF-α, tumor necrosis
factor-α; cfDNA, cell-free DNA; ctDNA, circulating tumor DNA;
KMT2D, lysine methyltransferase 2D; ALK, anaplastic lymphoma
kinase; miRNA/miR, microRNA; CTCs, circulating tumor cells; CSCs,
cancer stem cells; SPP1, secreted phosphoprotein 1
(osteopontin).
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Copy and paste a formatted citation
Spandidos Publications style
Li H, Fan W, Mu F, Fang C, Xiao T, Wan J and Cai H: Advances in cerebrospinal fluid biomarkers for the diagnosis, treatment and monitoring of leptomeningeal metastases (Review). Oncol Lett 31: 266, 2026.
APA
Li, H., Fan, W., Mu, F., Fang, C., Xiao, T., Wan, J., & Cai, H. (2026). Advances in cerebrospinal fluid biomarkers for the diagnosis, treatment and monitoring of leptomeningeal metastases (Review). Oncology Letters, 31, 266. https://doi.org/10.3892/ol.2026.15621
MLA
Li, H., Fan, W., Mu, F., Fang, C., Xiao, T., Wan, J., Cai, H."Advances in cerebrospinal fluid biomarkers for the diagnosis, treatment and monitoring of leptomeningeal metastases (Review)". Oncology Letters 31.6 (2026): 266.
Chicago
Li, H., Fan, W., Mu, F., Fang, C., Xiao, T., Wan, J., Cai, H."Advances in cerebrospinal fluid biomarkers for the diagnosis, treatment and monitoring of leptomeningeal metastases (Review)". Oncology Letters 31, no. 6 (2026): 266. https://doi.org/10.3892/ol.2026.15621
Copy and paste a formatted citation
x
Spandidos Publications style
Li H, Fan W, Mu F, Fang C, Xiao T, Wan J and Cai H: Advances in cerebrospinal fluid biomarkers for the diagnosis, treatment and monitoring of leptomeningeal metastases (Review). Oncol Lett 31: 266, 2026.
APA
Li, H., Fan, W., Mu, F., Fang, C., Xiao, T., Wan, J., & Cai, H. (2026). Advances in cerebrospinal fluid biomarkers for the diagnosis, treatment and monitoring of leptomeningeal metastases (Review). Oncology Letters, 31, 266. https://doi.org/10.3892/ol.2026.15621
MLA
Li, H., Fan, W., Mu, F., Fang, C., Xiao, T., Wan, J., Cai, H."Advances in cerebrospinal fluid biomarkers for the diagnosis, treatment and monitoring of leptomeningeal metastases (Review)". Oncology Letters 31.6 (2026): 266.
Chicago
Li, H., Fan, W., Mu, F., Fang, C., Xiao, T., Wan, J., Cai, H."Advances in cerebrospinal fluid biomarkers for the diagnosis, treatment and monitoring of leptomeningeal metastases (Review)". Oncology Letters 31, no. 6 (2026): 266. https://doi.org/10.3892/ol.2026.15621
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