We analyzed exosomal RNAs from longitudinally sampled plasma of osimertinib-treated EGFR T790M NSCLC patients in order to identify biomarkers of acquired drug resistance. RNA was subjected to transcriptomics analysis with Clariom D. While differential expression of 128 transcripts was detected, w further applied network enrichment analysis (NEA) at the pathway level. This revealed alterations in pathways related to EGFR and PI3K as well as to syndecan and glypican pathways. NEA then detected 16 immune-related gene sets. This demonstrated a potential usability of plasma-derived exosomal RNAs to characterize molecular phenotypes of emerging osimertinib resistance. Furthermore, it highlighted the prospects of creating multi-transcript diagnostic panels for monitoring treatment in NSCLC patients.
Andrey Alexeyenko, Odd Terje Brustugun, Inger Johanne Zwicky Eide, Radosveta Gencheva, Zeinab Kosibaty, Yi Lai, Luigi de Petris, Georgios Tsakonas, Oscar Grundberg, Bo Franzen, Kristina Viktorsson, Rolf Lewensohn, Per Hydbring, Simon Ekman Plasma RNA profiling unveils transcriptional signatures associated with resistance to osimertinib in EGFR T790M positive non-small cell lung cancer patients Transl Lung Cancer Res 2022;11(10):2064-2078. https://dx.doi.org/10.21037/tlcr-22-236
