Liquid biopsy and tumor DNA/RNA detection in the cerebrospinal fluid of patients diagnosed with central nervous system glioma – A review article
- Department of Neurosurgery, Hospital Universitário Evangelico de Curitiba, Curitiba, Parana, Brazil.
Irlon Oliveira, Department of Neurosurgery, Hospital Universitário Evangelico de Curitiba, Curitiba, Parana, Brazil.
DOI:10.25259/SNI_52_2023Copyright: © 2023 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
How to cite this article: Luis A. B. Borba, Gustavo Passos, Irlon Oliveira. Liquid biopsy and tumor DNA/RNA detection in the cerebrospinal fluid of patients diagnosed with central nervous system glioma – A review article. 26-May-2023;14:183
How to cite this URL: Luis A. B. Borba, Gustavo Passos, Irlon Oliveira. Liquid biopsy and tumor DNA/RNA detection in the cerebrospinal fluid of patients diagnosed with central nervous system glioma – A review article. 26-May-2023;14:183. Available from: https://surgicalneurologyint.com/surgicalint-articles/12336/
Background: Gliomas are the most common primary malignant neoplasms of the central nervous system and their characteristic genetic heterogeneity implies in a prominent complexity in their management. The definition of the genetic/molecular profile of gliomas is currently essential for the classification of the disease, prognosis, choice of treatment, and it is still dependent on surgical biopsies, which in many cases become unfeasible. Liquid biopsy with detection and analysis of biomarkers such as deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) from the tumor and circulating in the bloodstream or cerebrospinal fluid (CSF) has emerged as a minimally invasive alternative to aid in diagnosis, follow-up, and response to treatment of gliomas.
Methods: Through a systematic search in the PubMed MEDLINE, Cochrane Library, and Embase databases, we reviewed the evidence on the use of liquid biopsy to detect tumor DNA/RNA in the CSF of patients diagnosed with central nervous system gliomas.
Results: After a systematic review applying all inclusion and exclusion criteria, as well as a double review by independent authors, 14 studies specifically addressing the detection of tumor DNA/RNA in the CSF of patients diagnosed with central nervous system glioma were selected in the final analysis.
Conclusion: Sensitivity and specificity of liquid biopsy in CSF are still very variable depending on factors such as the diagnostic method, collection timing, biomarker (DNA and RNA), tumor type, extension and volume of the tumor, collection method, and contiguity from neoplasm to CSF. Despite the technical limitations that still exist and prevent the routine and validated use of liquid biopsy in CSF, the growing number of studies around the world is increasingly improving this technic, resulting in promising prospects for its use in diagnosis, evolutionary follow-up, and response to the treatment of complex diseases such as central nervous system gliomas.
Keywords: Cerebrospinal fluid, Circulating tumor DNA, Circulating Tumor RNA, Gliomas, Liquid biopsy
Central nervous system gliomas represent a complex and heterogeneous disease with multiple variants that affect from the pediatric age group to seniors. They represent about 25.1% of all primary tumors in the central nervous system and 80.8% of malignant brain tumors[
In this review, through a systematic search in PubMed databases MEDLINE, Cochrane Library, and Embase, we reviewed evidence from studies that address the application of liquid biopsy in the detection of tumor circulating DNA or RNA in the CSF of patients diagnosed with gliomas of the central nervous system.
The aim of the study was to assess the evidence on the effectiveness of liquid biopsy and detection of tumor DNA/ RNA in the CSF of patients with central nervous system gliomas.
Literature search strategy
The search was performed on PubMed MEDLINE, Cochrane Library, and Embase. The descriptors used in the formulation of the search strategy were defined based on the DECS/ MESH structured health vocabulary and systematized to increase the sensitivity of the initial research. The descriptors used were: “Liquid biopsy” [MeSH Terms] AND “CSF” [MeSH Terms] AND “circulating tumor DNA/CSF” [MeSH Terms] OR “circulating microrna/CSF” [MeSH Terms] OR “cell-free DNA” [MeSH Terms] OR “tumor derived DNA” [MeSH Terms] AND “glioma” [MeSH Terms] OR “glioma/ CSF” [MeSH Terms].
We do not set limits for the start date of publications, while to the final date, we established the limitation until October, 2021. After the initial research, two reviewers chose the relevant publications for the review based on the titles and abstracts found. Then, the full texts of the selected publications were reviewed to determine those compatible with the inclusion and exclusion criteria. In addition, we examined the references of the selected studies to verify the existence of other studies compatible with the search strategy but which were not included in the initial research.
Studies were selected according to the following inclusion criteria: studies with liquid biopsy in CSF, patients diagnosed with central nervous system gliomas, and studies in English language.
Studies were selected according to the following exclusion criteria: studies without availability of abstract, studies with other types of tumors, systematic reviews, meta-analyses, editorials, studies with exclusive blood plasma analysis, and animal studies.
Central nervous system gliomas represent complex neoplasms and mostly with a poor prognosis. The knowledge of its genetic heterogeneity has been decisive for the understanding of oncogenesis and consequently for the development of new treatment options and survival improvement. Liquid biopsy of CSF has emerged as a promising tool in the management of gliomas, providing information that helps in the diagnosis, definition of the genetic profile of the disease, and response to treatment.
In the pediatric subgroup, the importance and utility of liquid biopsy are highlighted due to the higher prevalence of midline gliomas, especially of the brain stem as these neoplastic subtypes usually imply difficulties for surgical biopsy, with limited treatment options and dismal prognosis.[
Although there are still many limitations and challenges, in recent years, the amount of research dedicated to the study of tumor biomarkers present in the CSF and improvement of diagnostic techniques has grown dramatically. It is known that tumor DNA/RNA is difficult to detect in CSF due to its fragmentation into small chains, short half-life,[
In our review, we found that the diagnostic sensitivity of liquid biopsy in CSF is still very variable depending on factors such as the diagnostic method, collection timing, biomarker (DNA, RNA), tumor type, extension and volume of the tumor, collection method, and contiguity from neoplasm to CSF.[
Although our review focused on analyzing the use of tumor DNA/RNA, we found that other biomarkers have shown promise in the CSF liquid biopsy of patients diagnosed with gliomas. Due to the relevance of the various biomarkers researched, below we highlight some characteristics of those most used today:
Circulating tumor DNA
Small fragments of 150–200 base pairs of tumor-derived DNA, circulating in the bloodstream or CSF and not coupled to cells.[
Circulating tumor RNA
This group includes micro-RNAs, long noncoding RNAs, and small non-coding RNAs.[
Both tumor cells and normal cells secrete EVs that carry diverse contents including proteins, lipids, DNA, and RNA that seem to perform functions of intercellular communication and regulation.[
Circulating tumor cells
Cells derived from the primary tumor and that enter the bloodstream or CSF are called circulating tumor cells.[
Genetic alterations in neoplasms such as gliomas alter the expression of cellular proteins and consequently define specific profiles that can be used as tumor biomarkers for diagnostic, therapeutic, and prognostic purposes.[
Through this review, we investigated the effectiveness of liquid biopsy and detection of tumor DNA/RNA in the CSF of patients diagnosed with gliomas of the central nervous system. The diagnostic sensitivity and specificity of liquid biopsy in CSF are still very variable depending on factors such as the diagnostic method, collection timing, biomarker (DNA and RNA), tumor type, extension and volume of the tumor, collection method, and contiguity from neoplasm to CSF. Despite the technical limitations that still exist and prevent the validated and routine use of liquid biopsy in CSF, the growing number of studies around the world increasingly improves it, resulting in promising perspectives for its use in diagnosis, evolutionary follow-up, and response to the treatment of complex diseases such as central nervous system gliomas.
Patient’s consent not required as there are no patients in this study.
There are no conflicts of interest.
The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Journal or its management. The information contained in this article should not be considered to be medical advice; patients should consult their own physicians for advice as to their specific medical needs.
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