New Method Uses Exosome Stiffness For Lung Cancer Gene Detection

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The investigation squad led by Senior Researchers Yoonhee Lee from nan Division of Biomedical Technology and Gyogwon Koo from nan Division of Intelligent Robot astatine DGIST (under President Kunwoo Lee) has developed a exertion that distinguishes lung crab cistron mutations solely by measuring nan "stiffness" of exosomes-tiny particles released from crab cells successful nan bloodstream-using atomic unit microscopy (AFM).

Their study enables accelerated and precise study of individual exosomes and is expected to beforehand into a caller liquid biopsy-based diagnostic method for lung cancer.

Non-small compartment lung crab (NSCLC) is nan astir communal type of lung cancer, accounting for much than 85% of each cases. However, because it seldom shows noticeable symptoms successful nan early stages, it is often diagnosed astatine an precocious stage, making curen difficult.

NSCLC continues to person a precocious mortality rate, and processing caller diagnostic technologies that alteration early discovery and curen remains a important situation successful nan aesculapian field. In particular, accepted insubstantial biopsies spot a sizeable load connected patients and person limitations successful repeated testing. As such, non-invasive liquid biopsy exertion utilizing blood-derived accusation has precocious attracted attention.

The investigation squad led by Senior Researchers Yoonhee Lee and Gyogwon Koo astatine DGIST isolated exosomes from NSCLC compartment lines pinch chopped genetic mutations (A549: KRAS mutation, PC9: EGFR mutation, PC9/GR: EGFR-resistant mutation). Using AFM, nan squad measured nano-scale beingness properties of individual exosomes astatine precocious resolution, including aboveground stiffness and height-to-radius ratios.

They recovered that nan exosomes derived from A549 cells exhibited importantly higher stiffness, which indicated that alterations successful nan compartment membrane lipids caused by KRAS mutations were besides reflected successful nan exosomes.

In contrast, exosomes derived from PC9 and PC9/GR cells showed akin properties, suggesting a relationship pinch their shared familial background. These findings show that nan beingness properties of exosomes alteration depending connected nan familial mutations of nan crab cells from which they originate.

To precisely categorize these nanomechanical characteristics of exosomes, nan investigation squad employed AI technology. Height and stiffness information of exosomes obtained done AFM were visualized and utilized to train a heavy learning-based convolutional neural web (DenseNet-121) exemplary to categorize their compartment lines of origin.

Exosomes derived from A549 cells were distinguished pinch a remarkably precocious accuracy of 96%, and nan wide mean AUC reached 0.92. This demonstrates nan imaginable of a next-generation liquid biopsy level tin of high-precision classification based solely connected nan beingness properties of exosomes, without nan request for fluorescent labeling.

Senior Researchers Yoonhee Lee and Gyogwon Koo stated, "This study presents a caller diagnostic imaginable to separate lung crab pinch circumstantial familial mutations utilizing only a mini magnitude of exosome samples. We scheme to actively prosecute nan applicable exertion of this exertion by integrating a high-speed AFM level successful objective sample validation."

Source:

Journal reference:

Park, S., et al. (2025). Deep Learning-Based Classification of NSCLC-Derived Extracellular Vesicles Using AFM Nanomechanical Signatures. Analytical Chemistry. doi.org/10.1021/acs.analchem.5c02009

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