Urine Tests Can Detect Brain Tumors by Using Nanowires to Capture Cancer DNA

Brain tumors are typically examined only after symptoms such as limb paralysis appear in the patient. By the time they are detected, they are usually so advanced that surgical removal poses a significant challenge. Among these tumors, gliomas are particularly lethal, with average survival rates ranging from 12 to 18 months. Consequently, early detection is vital for improving the patient's chances of survival. Given that patients regularly provide urine samples during routine physicals, these could potentially serve as a crucial source for identifying signs of brain tumors. One characteristic of brain tumors is the presence of cell-free DNA (cfDNA), minute DNA fragments released during the tumor's cell renewal process, and the disposal of old, damaged cells. Although the body's macrophages typically eliminate cfDNA, the rapid cell division in cancer results in surplus cfDNA, which ends up in the urine. However, the lack of techniques to efficiently isolate cfDNA from urine poses a challenge, as the excreted cfDNA can be short, fragmented, and low in concentration.

Researchers at Nagoya University (Nagoya, Japan) have now developed a technology to capture and release cfDNA from urine using nanowire surfaces. Through this DNA extraction, they were successful in detecting the IDH1 mutation, a distinctive genetic mutation associated with gliomas. This discovery enhances the efficacy of cancer detection tests using urine. The scientists employed a catch-and-release strategy using zinc oxide (ZnO) nanowire surfaces to collect cfDNA and extracellular vesicles from gliomas. They selected ZnO due to its ability to absorb water molecules on its nanowire surfaces, which then form hydrogen bonds with any cfDNA present in the urine sample. The bonded cfDNA can subsequently be flushed out, enabling the researchers to isolate even trace amounts from a sample. This technique proved to be a remarkable success.

“We succeeded in isolating urinary cfDNA, which was exceptionally difficult with conventional methods,” said Professor Takao Yasui, a member of the research group. “Although in a previous experiment, we showed that our nanowire could capture cancer extracellular vesicles, which we found in this sample too; the surprising thing was the capture of cfDNA using a similar technique. When we extracted the cfDNA, we detected the IDH1 mutation, which is a characteristic genetic mutation found in gliomas. This was exciting for us, as this is the first report of the detection of the IDH1 mutation from a urine sample as small as 0.5 ml.”

“This research overcomes the shortcomings of currently used methods by using chemical, biological, medical and nanotechnological techniques to provide a state-of-the-art method for the clinical use of urinary cfDNA, especially as an analytical tool to facilitate the early diagnosis of cancer,” Yasui said. “Although we tested gliomas, this method opens new possibilities for the detection of tumor mutations. If we know the type of mutation to look for, we can easily apply our technique to detect other types of tumors, especially the detection of those that cannot be isolated by conventional methods.”

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