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

Yukun Sun,Kok Suen Cheng,Kuang Hong Neoh,Junjie Tian,Baiye Jin,Xiaoyi Chen,Zhijie Xu,Yun Dai,Congcong Xu,Ray P S Han,Anqi Chen,Guanghou Fu

doi:10.3389/fonc.2021.701298

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.

Highlights

Bladder cancer is the second most common urogenital malignancy and ranks 13th in the death rate worldwide [1]
While around 80% patients were initially diagnosed with non-muscle invasive bladder cancer (NMIBC) [2], over 45% of them experienced tumor recurrence within 2 years and 6% worsen with increased tumor grade
This study showed microfluidic assay of circulating tumor cells (CTCs) holds the promise of a robust technique for the risk stratification of bladder cancer patients

Summary

Introduction

Bladder cancer is the second most common urogenital malignancy and ranks 13th in the death rate worldwide [1]. While around 80% patients were initially diagnosed with non-muscle invasive bladder cancer (NMIBC) [2], over 45% of them experienced tumor recurrence within 2 years and 6% worsen with increased tumor grade. Patients with bladder cancer require long-term monitoring and surveillance. Muscle invasiveness and tumor grade are the two critical prognostic factors that clinicians rely on in an attempt to individualize and provide effective treatments. Imaging techniques such as CT and MRI can provide preliminary information of the muscle invasiveness but are impeded by subjective judgement and lack of accuracy [6]. A timely and easy-to-perform complementary technique is highly necessary to reflect the risk stratification of bladder cancer patients

Methods

Results

Conclusion