Microfluidic Assaying of Circulating Tumor Cells and Its Application in Risk Stratification of Urothelial Bladder Cancer

Abstract

Bladder cancer is characterized by its frequent recurrence and progression. Effective treatment strategies need to be based on an accurate risk stratification, in which muscle invasiveness and tumor grade represent the two most important factors. Traditional imaging techniques provide preliminary information about muscle invasiveness but are lacking in terms of accuracy. Although as the gold standard, pathological biopsy is only available after the surgery and cannot be performed longitudinally for long-term surveillance. In this work, we developed a microfluidic approach that interrogates circulating tumor cells (CTCs) in the peripheral blood of bladder cancer patients to reflect the risk stratification of the disease. In a cohort of 48 bladder cancer patients comprising 33 non-muscle invasive bladder cancer (NMIBC) cases and 15 muscle invasive bladder cancer (MIBC) cases, the CTC count was found to be considerably higher in the MIBC group compared with the NMIBC group (4.67 vs. 1.88 CTCs/3 mL, P=0.019), and was significantly higher in high-grade bladder cancer patients verses low-grade bladder cancer patients (3.69 vs. 1.18 CTCs/3mL, P=0.024). This microfluidic assay of CTCs is believed to be a promising complementary tool for the risk stratification of bladder cancer.

A multifunctional black phosphorus nanosheet-based immunomagnetic bio-interface for heterogeneous circulating tumor cell capture and simultaneous self-identification in gastric cancer patients

“…However, since the number of CTCs in blood is extremely small, how to successfully and reliably capture them from the complex blood media is a critical step for downstream analysis. 7–12 Compared with the common capture methods established according to some physical properties, such as cell size, 13 density, 14 and permittivity, 15 an affinity-based strategy is more popularly employed in CTC isolation, taking advantage of the specific interactions between the recognition ligands (antibody, 16 aptamer, 17 peptide, 18 etc. ) on the capture interface and the biomarkers on the CTC membrane.…”

Circulating tumor cells correlating with Ki-67 predicts the prognosis of bladder cancer patients

“…The study concluded that postoperative CTC count is a useful biomarker for predicting the risk of tumor recurrence after liver transplantation. However, Fu et al [ 23 ] gave a different conclusion. The reasons considered were (1) residual CTCs in peripheral blood after bladder cancer surgery may be a major source of recurrence and metastasis after resection of the primary cancer and (2) due to the state of disease heterogeneity of the recruited patients (e.g.…”

Circulating Tumor Cells: Technologies and Their Clinical Potential in Cancer Metastasis

“…Following the approval and commercialization of CellSearch ® in 2008, numerous studies spanning a wide range of cancer types, including breast [ 11 , 15 , 16 , 22 , 25 , 26 , 30 , 32 , 33 , 39 , 40 ], colorectal [ 17 , 22 , 27 ], pancreatic [ 22 ], prostate [ 18 , 20 , 21 , 25 , 32 , 50 , 83 ], lung [ 24 , 28 ], melanoma [ 38 ], bladder [ 41 , 84 ], and gynecological [ 37 ] cancers have all confirmed a similar role for CTC enumeration within the clinical setting. The utility of CTC enumeration in stratifying patient prognosis may best be punctuated by a 2019 international expert consensus paper analyzing individual patient data from 18 cohorts encompassing 2436 mBC patients, confirming that stage IV mBC patients could be stratified into stage IV indolent and stage IV aggressive subtypes based solely on CTC count, independent of other clinical and molecular variables [ 39 ].…”