Urinary MicroRNA-Based Diagnostic Model for Central Nervous System Tumors Using Nanowire Scaffolds

There are no accurate
mass screening methods for early detection
of central nervous system (CNS) tumors. Recently, liquid biopsy has
received a lot of attention for less-invasive cancer screening. Unlike
other cancers, CNS tumors require efforts to find biomarkers due to
the blood–brain barrier, which restricts molecular exchange
between the parenchyma and blood. Additionally, because a satisfactory
way to collect urinary biomarkers is lacking, urine-based liquid biopsy
has not been fully investigated despite the fact that it has some
advantages compared to blood or cerebrospinal fluid-based biopsy.
Here, we have developed a mass-producible and sterilizable nanowire-based
device that can extract urinary microRNAs efficiently. Urinary microRNAs
from patients with CNS tumors (n = 119) and noncancer
individuals (n = 100) were analyzed using a microarray
to yield comprehensive microRNA expression profiles. To clarify the
origin of urinary microRNAs of patients with CNS tumors, glioblastoma
organoids were generated. Glioblastoma organoid-derived differentially
expressed microRNAs (DEMs) included 73.4% of the DEMs in urine of
patients with parental tumors but included only 3.9% of those in urine
of noncancer individuals, which suggested that many CNS tumor-derived
microRNAs could be identified in urine directly. We constructed the
diagnostic model based on the expression of the selected microRNAs
and found that it was able to differentiate patients and noncancer
individuals at a sensitivity and specificity of 100 and 97%, respectively,
in an independent dataset. Our findings demonstrate that urinary microRNAs
extracted with the nanowire device offer a well-fitted strategy for
mass screening of CNS tumors.