Yonsei University team develops technology to detect multiple cancer signals in urine simultaneously

A research team led by Professor Shin Yong at Yonsei University's Department of Biotechnology has developed a groundbreaking molecular diagnostic platform capable of simultaneously analyzing multiple cancer-related microRNAs (miRNAs) in urine. This innovative technology converts changes in the binding orientation of DNA nanostructures upon encountering specific miRNAs into detectable light signals (SERS).

MicroRNAs (miRNAs) are gaining attention as biomarkers for various diseases, including cancer, due to their altered levels in affected individuals. miRNAs found in extracellular vesicles within urine or blood offer a promising avenue for non-invasive disease diagnosis, reducing the burden associated with blood draws or tissue biopsies. However, existing analysis methods often necessitate separate amplification steps and become procedurally complex when analyzing multiple miRNAs simultaneously.

To overcome these limitations, the research team developed the 'Dual Tetrahedral DNA Orientation-SERS (DTO-SERS)' platform. This system employs two tetrahedral DNA nanostructures. When a specific miRNA connects these structures, they bind in different orientations. The resulting variation in the binding direction and distance, dependent on the type of miRNA, alters the SERS signal, allowing for differentiation.

The team further enhanced the platform's reliability by building a four-channel system capable of simultaneously analyzing three prostate cancer-related miRNAs and a reference RNA (RNU48). Using RNU48 as a baseline helps correct signal variations caused by measurement location or sample differences, thereby improving analytical accuracy and reproducibility.

To validate the platform's potential, the researchers analyzed urine samples from 20 individuals, including 15 prostate cancer patients and 5 non-cancer controls. They observed distinct patterns in the levels of the three prostate cancer-related miRNAs, with some showing increased presence and others decreased in cancer patients. Analyzing all three miRNAs together demonstrated the potential to distinguish between prostate cancer patients and healthy individuals.

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This research is significant in that it utilized DNA nanostructures not just as a support, but as a signal conversion device whose structure and orientation change depending on the target. By simultaneously measuring multiple miRNAs and reference RNAs without nucleic acid amplification, it is expected to be expanded into various multiplex biomarker analysis technologies, including non-invasive cancer diagnosis in the future.