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Christina Lau, 14 Feb 2019
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Audrey Abella, 28 Aug 2019
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Liquid biopsy a promising tool for establishing diagnosis in GBM patients

Dr. Joseph Delano Fule Robles
17 May 2019

Liquid biopsy is demonstrated to be a quick, inexpensive diagnostic modality that can be performed multiple times to help establish a diagnosis of glioblastoma multiforme (GBM) without high-risk neurosurgical interventions.

GBM’s remarked intratumoural heterogeneity and diffuse infiltrative nature result in unfavourable clinical consequences.  [Proc Natl Acad Sci USA 2013;110:4009-4014] Recent categorization of GBM based on gene expression profile as neural, proneural, mesenchymal or classic has made integration of histopathological findings and molecular alterations possible, leading to its possible utility in the clinics as prognostic and predictive markers. [J Biotechnol 2019;298:82-87; Cancer Cell 2010;17:510-522]

Liquid biopsy involves using serum, cerebrospinal fluid (CSF) and urine samples to detect tumour components such as extracellular vesicles (EVs), circulating cell-free coding and non-coding nucleic acids (cf-NAs), microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). These components are involved in intercellular communication, tumour suppression and epigenetic regulation. [Non-coding RNA 2018, doi: 10.3390/ncrna5010001; Neuro Oncol 2015;17:343-360; Acta Neuropathol 2015;129:849-865]

Refinements during follow-ups and repeated sample collections may also be performed, as opposed to the traditional way of obtaining samples via surgical resection or biopsy. [Curr Neurol Neurosci Rep 2016;16:25; Cell 2016;120:635-647; Curr Neurol Neurosci Rep 2018;18:13]

cf-deoxyribonucleic acids (cf-DNAs) are 70-200 base pairs composed mainly of genomic DNA and are released during necrosis or apoptosis. EVs contain these nucleic acids and can be transferred intercellularly. Some cf-DNAs with known molecular alterations in GBM have been investigated, but their significance is still inconclusive. [Eur J Hum Genet 2018;26:937-945; Oncotarget 2016;7:65888-65901]

A number of miRNAs (miR-128 and miR-342-3p) function as tumour suppressors and are demonstrated to be downregulated in GBM patients. Downregulation of these miRNAs triggers angiogenesis, self-renewal, and proliferation of GBM cells by targeting p70s6k146, Bmi-147, E2F3a48 and receptor tyrosine kinases (RTKs). [Int J Clin Exp Med 2015;8:456; J Mol Med 2009;87:43-51]

Overexpression of miR-221/222 and miR-454-3p in serum were demonstrated to be associated with low survival rates in GBM patients. [Curr Mol Med 2014;14:185-195; Neurol Sci 2015:36;309-313] Moreover, miR-21, miR-218, miR-193b, miR-331, and miR-374a were found to be overexpressed, while miR-548c, miR-520f, miR-27b, and miR-130b were downregulated in GBM CSF vs control CSF samples. [Oncotarget 2017;8:68769-68779]

lncRNAs are responsible for post-translational level gene expression and epigenetic regulation. Among these, HOTAIR, MALAT1 and GAS5 were demonstrated to be detectable in tumour and serum samples of GBM patients. [Genomics, Proteomics Bioinformatics 2016:14:42-54; Metab Brain Dis 2017;32:281-291]

Despite its significance and its possible clinical application, there is currently no consensus among experts as to what type of nucleic acids, biologic fluids or analytical technique would be worth investigating the most. [Clin Oncol 2017;14:531-548]

GBM is the most common primary malignant tumour of the brain, which makes up almost half of all cases of primary malignant central nervous system neoplasms. With its highest rate in individuals aged 75–84 years, poor median overall survival of 16–24 months and 5-year survival rate of 5.6 percent, it remains one the most fatal neoplastic disorder. [Neuro Oncol 2018;20(Suppl4);iv1-iv86]

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Most Read Articles
Christina Lau, 14 Feb 2019
Progress in the treatment of rare cancers has been named Advance of the Year by the American Society of Clinical Oncology (ASCO).
Pearl Toh, 28 Aug 2019
The addition of radium-223 (Ra223) to enzalutamide for the treatment of mCRPC* was associated with increased fracture risk, which was entirely abolished with mandated use of bone-protecting agents (BPAs) such as zoledronic acid and denosumab, according to interim results of the EORTC 1333 (PEACE III) trial.
Audrey Abella, 28 Aug 2019
A pooled analysis of six trials failed to show noninferiority of a 3-month regimen to a 6-month regimen of oxaliplatin-based chemotherapy for patients with high-risk, stage II colorectal cancer (CRC).