Abstract
Objectives: Tumor cells were reported to have perpetual negative surface charges due to elevated glycolysis, and multifunctional nanoprobes (Fe3O4@SiO2, mNPs) could attach onto tumor cells via opposite surface charges. We thus evaluated whether mixing mNPs with urine could improve the sensitivity of urine cytology test (UCT). Methods: We developed a novel UCT method by mixing urine with mNPs (Nano-cytology) to harvest more tumor cells during UCT procedures. The same voided urine sample was divided equally for the Nano-cytology and UCT assay, and evaluated by cytopathologists in a blinded way. The accuracy of UCT, Nano-cytology, and the combination of the two approaches (Nano-UCT) for detecting bladder cancer were determined. Results: Urine samples were prospectively collected from 102 bladder cancer patients and 49 non-cancer participants from June 2020 to February 2021 in Changhai Hospital. Overall sensitivity of the Nano-cytology assay was significantly higher than that of the UCT assay (82.4 vs. 59.8%, p < .01). Sensitivity for low- and high-grade tumors was 79.1% and 39.5% (p < .01) and 84.7% and 74.6% (p = .25) for Nano-cytology and UCT, respectively. Specificity of Nano-cytology was slightly lower than that of UCT (89.8% vs. 100%, p = .022), which is mainly caused by severe urinary tract infection. In addition, Nano-UCT showed increased sensitivity with 90.2% for overall patients, and 83.7% and 94.9% for low- and high-grade tumor, respectively. Conclusion: The Nano-cytology assay had a significantly improved sensitivity compared with UCT for detecting bladder cancer patients. It represents a promising tool for diagnosis of bladder cancer in clinical practice.
Highlights
Bladder cancer (BC) is the 10th most commonly diagnosed cancer worldwide (International Agency for Research on Cancer, 2021)
Detailed procedures to construct mNPs were described in a previous study, and all the mNPs used in the present study were synthesized by The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine (Chen et al, 2016)
We tried to characterize the interaction of the bladder cancer cell and mNPs; a constant number of three different bladder cancer cells were incubated with various concentrations of positively charged mNPs ranging from 5 to 150 μg/ml, and with 50 μg/ml mNPs at different pH
Summary
Bladder cancer (BC) is the 10th most commonly diagnosed cancer worldwide (International Agency for Research on Cancer, 2021). 75% of patients with BC present with non-muscleinvasive bladder cancer (NMIBC) (Compérat et al, 2015). Cystoscopy and urine cytology are the most important examinations for both diagnosis and surveillance of BC. Numerous non-invasive urine biomarkers have been developed for diagnosis of UC, urine cytology test (UCT) is the only recommended liquid biopsy for surveillance of BC in different treatment guidelines for BC (Witjes et al, 2021). LCT (liquid-based cytology test) is commonly used in UCT daily practice with the advantages of being specific and non-invasive, but LCT depends on the experience of cytopathologists and the sensitivity is unsatisfactory, varying from 29% to 84% for different grades of BC, especially lower for low-grade BC (Yafi et al, 2015; Babjuk et al, 2022). There is a clinical need to decrease the technique difficulty of LCT and improve its sensitivity
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