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Take a look at a selection of our recent media coverage:

Urine microRNA profile a biomarker for brain tumours

22nd June 2021

Mass screening of urine for a unique microRNA biomarker profile could represent means of early detection for brain tumours.

Few people undergo routine brain scans to help identify potential early signs of a tumour. While imaging modalities such as MRI and CT are a very sensitive and effective means of testing, these are expensive and thus unsuitable for mass screening. Nevertheless, the detection of shed tumour components such as DNA or cellular fragments into the general circulation could be used for the early detection of a tumour. The use of microRNAs, i.e., small and non-coding fragments of RNA, in blood samples has already been utilised of early detection of breast, ovarian and bladder cancers. However, urine-based detection of microRNAs offers some advantages over blood samples in so far as these can be self-performed and repeated with minimal effort. The use of urine-based methods has yet to be explored in detail and this was the subject of a study by a team from the Department of Neurosurgery, Graduate School of Medicine, Nagoya, Japan. The researchers developed a device that contained 100 million zinc oxide nanowires, that could be sterilised and equally importantly, mass produced. The device required only 1 ml of urine but was able to extract a much larger number of microRNAs compared to ultracentrifugation, which is the most commonly used extraction device. The researchers examined urine samples from patients with and without brain tumours and used microarray analysis to determine whether there was a specific and diagnostic microRNA profile that could be used as a biomarker.

Findings
The researcher used urine samples from 109 patients with a brain tumour and compared the microRNA profile with 100 non-cancer patients. Initially, the team used organoids (i.e., a collection of cells) from glioblastoma, an aggressive form of brain tumour, to determine the profile of urinary microRNAs likely to be produced by patients with the tumour. The analysis revealed how the glioblastoma organoid-derived sample differentially expressed microRNAs, included 73.4% of the microRNAs found in the urine samples of patients with glioblastoma. In comparison, this microRNA profile was produced in only 3.9% of the non-cancer patient samples.

Having established that this profile, which contained 23 separate microRNAs, was characteristically produced in patients with glioblastoma, the researchers sought to determine if the profile could serve as a biomarker. Using the area under the receiver operator curves, the profile produced a sensitivity of 100% and a specificity of 97%.

Based on these findings, the authors concluded that this specific microRNA profile, could potentially be used for mass screening purposes for the early detection of potentially aggressive brain tumours.

Citation
Kitano Y et al. Urinary MicroRNA-Based Diagnostic Model for Central Nervous System Tumours Using Nanowire Scaffolds. ACS Appl Mater interfaces 2021;13:17316 – 17329

MicroRNAs can distinguish between myocarditis and myocardial infarction

11th June 2021

Myocarditis can mimic myocardial infarction but a unique biomarker provides clinicians an opportunity to distinguish the two conditions.

Acute myocarditis (aMC) has many different causes but the prevalence is unclear because the condition has similar clinical symptoms to an acute myocardial infarction (aMI). Although the diagnosis of myocarditis can be confirmed with cardiac magnetic resonance imaging, this technique is not always available. However, one approach to resolve the diagnosis involves the use of microRNAs (miRNAs), which are small, non-coding RNAs that play an important role in gene expression. Several miRNAs have been identified in the infarcted heart and this led a team from the Vascular Pathophysiology Area, Madrid, to try and identify a unique miRNA which could be used to distinguish between myocarditis and myocardial infarction. The team focused on circulating T cells, in particular T helper 17 (Th17) cells, which were confirmed as being a characteristic of myocardial injury in the acute phase of myocarditis. They performed a miRNA microarray analysis and quantitative polymerase chain reaction (qPCR) assays in Th17 cells after experimentally inducing myocarditis and myocardial infarction in mice to identify unique biomarkers.

Findings
The researchers identified the miRNA, mmu-miR-721, produced by Th17 cells in mice which was only produced in response to either autoimmune or viral myocarditis and which was absent from those with aMI. Using four patient cohorts with myocarditis, they subsequently identified a human homologue to mmu-miR-721, termed has-miR-Chr8:96. The researchers found that plasma levels of has-miR-Chr8:96 were considerably higher among myocarditis patients compared to both those with a myocardial infarction and in healthy controls. The area under the receiver-operating characteristics curve for has-miR-Chr8:96 was 0.927 (i.e., 92.7%) for distinguishing between aMC and aMI and this diagnostic value was retained even after adjusting for age, ejection fraction, and serum troponin levels.

Although the authors accepted that more work is needed to validate this biomarker in other cardiac disorders such as dilated cardiomyopathy, their preliminary findings suggest that raised plasma levels of has-miR-Chr8:96 are unique to those with myocarditis and have sufficient discriminatory power from myocardial infarction.

Citation
Blanco-Dominguez R et al. A Novel Circulating MicroRNA for the Detection of Acute Myocarditis. N Engl J Med 2021;384:2014-27