RESUMEN
Correction for 'Plasma extracellular vesicle phenotyping for the differentiation of early-stage lung cancer and benign lung diseases' by Liwen Yuan et al., Nanoscale Horiz., 2023, 8, 746-758, https://doi.org/10.1039/d2nh00570k.
RESUMEN
The development of a minimally invasive technique for early-stage lung cancer detection is crucial to reducing mortality. Phenotyping of tumor-associated extracellular vesicles (EVs) has the potential for early-stage lung cancer detection, yet remains challenging due to the lack of sensitive, integrated techniques that can accurately detect rare tumor-associated EV populations in blood. Here, we integrated gold core-silver shell nanoparticles and nanoscopic mixing in a microfluidic assay for sensitive phenotypic analysis of EVs directly in plasma without EV pre-isolation. The assay enabled multiplex detection of lung cancer-associated markers PTX3 and THBS1 and canonical EV marker CD63 by surface-enhanced Raman spectroscopy, providing a squared correlation coefficient of 0.97 in the range of 103-107 EVs mL-1 and a limit of detection of 19 EVs mL-1. Significantly, our machine learning-based nanostrategy provided 92.3% sensitivity and 100% specificity in differentiating early-stage lung cancer from benign lung diseases, superior to the CT scan-based lung cancer diagnosis (92.3% sensitivity and 71.4% specificity). Overall, our integrated nanostrategy achieved an AUC value of 0.978 in differentiating between early-stage lung cancer patients (n = 28) and controls consisting of patients with benign lung diseases (n = 23) and healthy controls (n = 26), which showed remarkable diagnostic performance and great clinical potential for detecting the early occurrence of lung cancer.
Asunto(s)
Vesículas Extracelulares , Neoplasias Pulmonares , Humanos , Biomarcadores de Tumor , Neoplasias Pulmonares/diagnóstico , Vesículas Extracelulares/química , Plasma , Detección Precoz del Cáncer/métodosRESUMEN
Isatin is an endogenous indole in mammalian tissues and fluids that is expected to have antitumor effects in human breast cancer cells. Human breast cancer cells (MCF-7) were exposed to isatin at various concentrations (0, 50, 100, 200 µmol/l) for 48 h. Apoptotic features were demonstrated by nuclei staining with Hoechst 33258 and flow cytometry. Bcl-2 and Bax mRNA were analyzed via reverse transcription-polymerase chain reaction. Bcl-2, Bax, the inhibitor of caspase-activated DNase (ICAD), and cytochrome c protein were analyzed by western blot analysis. Apoptosis, caspase-9 and -3 activation and mitochondrial depolarization were assayed by flow cytometry. The results showed that isatin induced apoptosis of MCF-7 cells. Furthermore, Bcl-2 expression was decreased and the ratio of Bcl-2 to Bax was significantly decreased by isatin. The mitochondrial transmembrane potential was markedly decreased and the release of cytochrome c into the cytosol was elevated following treatment with isatin. At the same time, caspase-9 and -3 were stimulated, followed by the degradation of ICAD, a caspase-3 substrate.