A new immunomagnetic microfluidic device for characterizing EGFR mutations in circulating tumor cells from patients withnon-small cell lung cancer

Ogidi, Nkeiruka O.; Lind, Michael J.; Greenman, John

Abstract

ncorporating precision oncology into cancer management has begun to improve clinical outcomes. Accurate sampling techniques that detect molecular aberrations are crucial for effective implementation. Circulating tumor cells (CTCs), derived from primary or metastatic sites and present in the blood, are proposed as useful diagnostic tools, though their use has been limited due to their rarity, especially in early-stage cancers. This study presents a novel immunomagnetic microfluidic device that efficiently isolates CTCs for analyzing epidermal growth factor receptor (EGFR) mutations in patients with non-small cell lung cancer (NSCLC). The device was designed and laser-cut from polymethylmethacrylate. Validation experiments involved spiking PC-9 cells (an established lung cancer cell line containing GLU 746-ALA 750 deletion mutations in exon 19 of the EGFR gene) into media and isolating these cells. Exons 18 – 21 of EGFR were amplified using a polymerase chain reaction to demonstrate the device’s rapid mutation detection capability. Next-generation sequencing was used to characterize these exons in a cohort of 38 NSCLC patients, successfully isolating CTCs from all. Among these patients, 30 (79%) had EGFR mutations, with exon 19 showing the highest mutation rate (87%) and exon 21 the highest point mutation rate (23%). Our device captured CTCs effectively in <1 h, enabling mutation detection. Further studies are needed to assess the prognostic significance of these mutations, but this technology has potential applications in various solid tumors.

Citation

Ogidi, N. O., Lind, M. J., & Greenman, J. (online). A new immunomagnetic microfluidic device for characterizing EGFR mutations in circulating tumor cells from patients withnon-small cell lung cancer. Tumor Discovery, Article 3987. https://doi.org/10.36922/td.3987

• Journal Article Type: Article
• Acceptance Date: Sep 19, 2024
• Online Publication Date: Nov 12, 2024
• Deposit Date: Nov 26, 2024
• Publicly Available Date: Nov 28, 2024
• Journal: Tumor Discovery
• Print ISSN: 3060-8597
• Electronic ISSN: 2810-9775
• Peer Reviewed: Peer Reviewed
• Article Number: 3987
• DOI: https://doi.org/10.36922/td.3987
• Keywords: Precision oncology; CTC; NSCLC; EGFR; Microfluidics; Immunomagnetic
• Public URL: https://hull-repository.worktribe.com/output/4926963