Urine miRNA Testing Reveals CNS Tumors

Brain cancer, artwork
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Early diagnosis of CNS tumors is complicated by the lack of early symptoms. Brain CT or MRI are definitive, but usually done only after the onset of noticeable symptoms when the cancer has spread or is otherwise inoperable due to a large tumor size.

A study from Nagoya University found that urine testing for microRNAs could be a promising biomarker to diagnose central nervous system (CNS) tumors.

“Urine-based liquid biopsy has not been fully investigated for patients with non-urological tumors because none of the conventional methodologies (e.g., ultracentrifugation and polymeric precipitation methods like ExoQuick-TC) have a satisfactory way to collect urinary miRNAs,” the authors write in their paper in ACS Applied Materials & Interfaces.

The team developed a new device for that purpose.  The sterilizable and mass-producible zinc oxide nanowire-based device requires one ml of urine to produce a result. Studies revealed the device was capable of extracting a greater variety and quantity of urinary miRNAs compared to ultracentrifugation and ExoQuick-TC. The miRNAs identified by ultracentrifugation accounted for less than 1% of the total while miRNAs identified by the nanowire device accounted for more than 50%.

The researchers created CNS tumor organoids to clarify the origin of urinary miRNA characteristics of patients with these sorts of tumors. Using the new device, they extracted miRNAs from the urine and culture supernatants of these CNS tumor-derived organoids to identify the miRNA types.

“Microarray analysis of urinary miRNAs revealed a characteristic miRNA expression pattern, and based on it, we constructed a diagnostic model of patients with CNS tumors,” the authors write.

Next, they extracted and analyzed miRNAs from the urine of noncancer patients and individuals with CNS tumors to see if they could identify stable CNS-based miRNAs.

The results showed that the model can distinguish the patients from individuals without cancer at a sensitivity of 100% and a specificity of 97%.  “Our diagnostic model could accurately detect CNS tumors irrespective of the tumor grade and size, which demonstrates that it is an ideal screening method for CNS tumors,” they write.

On the basis of the microarray results, the team identified a total of 57 miRNAs that showed significantly higher or lower expression in the patients with CNS tumors compared to healthy controls in the training set; 22 miRNAs were upregulated and 35 miRNAs were downregulated in patients with CNS tumors. The researchers believe urinary miRNA expression may also reflect slight changes in the tumor itself such as malignant transformation.

Further analysis revealed a 23-set of miRNAs as a starting point for a diagnostic CNS test. “In the future, examining only 23 miRNAs selected for the diagnostic model in this study will allow diagnosis of CNS tumors by non-expensive methods such as real-time reverse transcription polymerase chain reaction (PCR),” they write.

The team hopes that their findings will contribute to early diagnosis of aggressive types of brain cancer, like glioblastomas, as well as other types of cancer. Says Nagoya University Associate Professor Atsushi Netsuke, a corresponding author of the study, “In the future, by a combination of artificial intelligence and telemedicine, people will be able to know the presence of cancer, whereas doctors will be able to know the status of cancer patients just with a small amount of their daily urine.”

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