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STUDY. Brain cancers could be identified early by a new method that analyzes membrane proteins in urine

Certain membrane proteins in urine may indicate an early brain tumor, according to a study published in ACS Nano by specialists at Nagoya University in Japan. With the help of a new device, All-in-One Nanowire Assay System (an integrated system capable of analyzing the tumor microenvironment mediated by extracellular vesicles excreted in the urine), two specific types of membrane proteins were identified in the urine samples of patients with brain tumors – CD31/CD63. Moreover, their expression ratio was 2.25 times higher in urine samples from patients with glioblastom than in those without cancer.

Despite advances in early cancer detection, the survival rate for brain tumors has remained nearly unchanged for over 20 years. Only 36% of patients with malignant brain tumors survive more than five years, according to the American Cancer Society. The low survival rate is also partly determined by late diagnosis. By the time neurological symptoms appear, such as difficulty in movement and speech, the disease is already in an advanced stage and the tumor is large, which makes it inoperable.

Extracellular vesicles (EVs) are nanometer membrane vesicles, which contain nucleic acids, proteins, bioactive lipids and ensure intercellular communication and regulation of cellular function. Malignant cells are known to have a higher amount of VEs with disease-related genetic and proteomic information than normal cells, which has made VEs study targets to become predictive biomarkers in the occurrence of certain types of cancer. Because VEs of brain cancer patients have specific types of RNA and membrane proteins, they could be used to detect the presence of cancer and its progression.

A possible sign that a person has a brain tumor is the presence of tumor-specific extracellular vesicles in the urine. Although excreted at a distance from the brain tissue, many VE from malignant cells are stable and are found in the urine intact. Urine testing has many advantages, according to Prof. Takao Yasui from Nagoya University: “Liquid biopsy can be performed using many body fluids, but blood tests are invasive. Urine tests are an effective, simple and non-invasive method, as urine contains many clinically relevant biomolecules that can be tracked to provide information on disease progression.”

“Currently, methods for isolating and detecting VE require more than two instruments and one test to isolate and then detect. The all-in-one nanowire assay can isolate and detect VE using one simple procedure. In the future, users can run samples through our assay and change the detection part, selectively modifying it to detect specific membrane proteins or microRNAs inside VEs to detect other cancers. Using this platform, we expect to advance the analysis of the expression levels of specific membrane proteins in VEs from patients’ urine, which will enable early detection of various types of cancer,” added Prof. Yasui.

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