Clinical validation of a size-based microfluidic device for circulating tumor cell isolation and analysis in renal cell carcinoma

• Published in: International journal of molecular sciences Vol. 24; no. 9; p. 8404
• Main Authors: Palmela Leitão, Tito, Martins Corredeira, Patrícia Isabel, Kucharczak, Sandra, Rodrigues, Margarida, Piairo, Paulina, Rodrigues, Carolina, Alves, Patrícia, Martins Cavaco, Ana Cláudia, Miranda, Miguel, de Sousa Antunes, Marilia Cristina, Ferreira, João, Palma dos Reis, José Manuel, Lopes, Tomé, Diéguez, Lorena, Costa, Luis
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 07.05.2023; MDPI AG
• Subjects: Biomarkers; Biomarkers, Tumor - metabolism; Biopsy; Blood; Carcinoma, Renal Cell; Cell Line; Cells; Circulating tumor cell; Disease management; Efficiency; FDA approval; Health services; Humans; Kidney cancer; Kidney Neoplasms - pathology; Liquid biopsy; Metastases; Metastasis; Microfluidic; Microfluidic devices; Microfluidics; Neoplastic Cells, Circulating - pathology; Patients; Renal cell carcinoma; Scientific equipment and supplies industry; Stem cells; Tumor cells; Tumors; United States; Portugal; North America; kidney cancer; circulating tumor cell; renal cell carcinoma; microfluidic; liquid biopsy
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24098404

© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Renal cell carcinoma (RCC) presents as metastatic disease in one third of cases. Research on circulating tumor cells (CTCs) and liquid biopsies is improving the understanding of RCC biology and metastases formation. However, a standardized, sensitive, specific, and cost-effective CTC detection technique is lacking. The use of platforms solely relying on epithelial markers is inappropriate in RCC due to the frequent epithelial-mesenchymal transition that CTCs undergo. This study aimed to test and clinically validate RUBYchip™, a microfluidic label-free CTC detection platform, in RCC patients. The average CTC capture efficiency of the device was 74.9% in spiking experiments using three different RCC cell lines. Clinical validation was performed in a cohort of 18 patients, eight non-metastatic (M0), five metastatic treatment-naïve (M1TN), and five metastatic progressing-under-treatment (M1TP). An average CTC detection rate of 77.8% was found and the average (range) total CTC count was 6.4 (0-27), 101.8 (0-255), and 3.2 (0-10), and the average mesenchymal CTC count (both single and clustered cells) was zero, 97.6 (0-255), and 0.2 (0-1) for M0, M1TN, and M1TP, respectively. CTC clusters were detected in 25% and 60% of M0 and M1TN patients, respectively. These results show that RUBYchip™ is an effective CTC detection platform in RCC.