Microfluidic Analysis of Captured Urinary Exfoliated Tumor Cells - Expert Commentary

Due to the very high risk of recurrence, bladder cancer patients require periodic screening and monitoring. Due to the invasiveness and cost of the currently used tools like cystoscopy, the low sensitivity of urine cytology and the lack of sensitivity and specificity of the recent molecular techniques (BTA and NMP22), there is an unmet clinical need for less invasive and more sensitive and specific methods to detect UBC. 

A recent study published in Cancer Research by Chen et al. introduced a new microfluidic immunoassay to detect bladder cancer by detecting cells with a CK20 and CD44v6 phenotypes simultaneously to identify the urinary-exfoliated tumor cells (UETCs). CK20 is an intermediate filament protein and CD44v6 is a membrane adhesion molecule. These are oncoproteins enhanced in UETCs and used as biomarkers for bladder cancers.

The investigators collected urine samples from two age matching groups (79 bladder cancer patients and 43 normal controls). Single-cell whole-genome sequencing on 12 captured UETCs and copy number alteration analysis showed that 11/12 (91.7%) of the immunofluorescence-identified UETCs possessed genomic instability. The investigators found that the UETC counts were significantly higher in BC patients than NC through ROC analysis with an area under the curve of 0.85 with 89.9% sensitivity and 71.5% specificity. UETCs count was higher in higher-grade bladder cancer and larger tumors. There was no significant difference between the UETCs count and the invasiveness, recurrence or multi-focality of the cancer. Paired comparisons between microfluidic immunoassay and traditional cytology showed a more than 2-fold higher sensitivity difference. 

This study represents an important advance in the area of developing improved urine tests for the detection of bladder cancer. 

Written by: Bishoy M. Faltas, MD, Weill Cornell Medicine, New York, NY

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