posted on 2024-02-09, 23:03authored byJunhee Han, Jik-Han Jung, Sung Yong Lee, Ji-Ho Park
Analysis of membrane proteins from extracellular vesicles
(EVs)
has emerged as an important strategy for molecular cancer diagnosis.
The epidermal growth factor receptor (EGFR) is one of the most well-known
oncogenic membrane proteins, particularly in non-small cell lung cancer
(NSCLC), where targeted therapies using tyrosine kinase inhibitors
(TKIs) are often addressed based on EGFR mutation status. Consequently,
several studies aimed at analyzing oncogenic membrane proteins have
been proposed for cancer diagnosis. However, conventional protein
analysis still faces limitations due to the requirement for large
sample quantities and extensive post-labeling processes. Here, we
develop a nanoplasmonic detection method for EGFR mutations in the
diagnosis of NSCLC based on interactions between EGFR loaded in EVs
and TKI. Gefitinib is selected as a model TKI due to its strong signals
in the surface-enhanced Raman spectroscopy (SERS) and mutation-dependent
binding affinity to EGFR. We demonstrate an SERS signal attributed
to gefitinib at a higher value in the EGFR exon 19 deletion, both
in cells and EVs, compared to wild-type and exon 19 deletion/T790M
variants. Furthermore, we observe a significantly higher gefitinib
SERS signal in EGFR obtained from exon 19 deletion NSCLC patient plasma-derived
EVs compared with those from wild-type and exon 19 deletion/T790M
EVs. Since our approach utilizes an analysis of the SERS signal generated
by the interaction between oncogenic membrane proteins within EVs
and targeted drugs, its diagnostic applicability could potentially
extend to other liquid biopsy methods based on EVs.