TY - JOUR
TI - Gene expression in circulating tumor cells reveals a dynamic role of EMT and PD-L1 during osimertinib treatment in NSCLC patients
AU - Ntzifa, A.
AU - Strati, A.
AU - Kallergi, G.
AU - Kotsakis, A.
AU - Georgoulias, V.
AU - Lianidou, E.
JO - Scientific Reports
PY - 2021
VL - 11
TODO - 1
SP - null
PB - Institute of Geographic Sciences and Natural Resources Research
SN - 2045-2322
TODO - 10.1038/s41598-021-82068-9
TODO - axl receptor tyrosine kinase;  complementary DNA;  oncoprotein;  protein kinase Pim 1;  protein tyrosine kinase;  Twist related protein 1;  VIM protein, human;  vimentin, female;  fluorescent antibody technique;  genetics;  human;  immunology;  male;  metabolism;  non small cell lung cancer;  tumor embolism, Aldehyde Dehydrogenase 1 Family;  Carcinoma, Non-Small-Cell Lung;  DNA, Complementary;  Female;  Fluorescent Antibody Technique;  Humans;  Male;  Neoplastic Cells, Circulating;  Proto-Oncogene Proteins;  Proto-Oncogene Proteins c-pim-1;  Receptor Protein-Tyrosine Kinases;  Twist-Related Protein 1;  Vimentin
TODO - Liquid biopsy is a tool to unveil resistance mechanisms in NSCLC. We studied changes in gene expression in CTC-enriched fractions of EGFR-mutant NSCLC patients under osimertinib. Peripheral blood from 30 NSCLC patients before, after 1 cycle of osimertinib and at progression of disease (PD) was analyzed by size-based CTC enrichment combined with RT-qPCR for gene expression of epithelial (CK-8, CK-18, CK-19), mesenchymal/EMT (VIM, TWIST-1, AXL), stem cell (ALDH-1) markers, PD-L1 and PIM-1. CTCs were also analyzed by triple immunofluorescence for 45 identical blood samples. Epithelial and stem cell profile (p = 0.043) and mesenchymal/EMT and stem cell profile (p = 0.014) at PD were correlated. There was a strong positive correlation of VIM expression with PIM-1 expression at baseline and increased PD-L1 expression levels at PD. AXL overexpression varied among patients and high levels of PIM-1 transcripts were detected. PD-L1 expression was significantly increased at PD compared to baseline (p = 0.016). The high prevalence of VIM positive CTCs suggest a dynamic role of EMT during osimertinib treatment, while increased expression of PD-L1 at PD suggests a theoretical background for immunotherapy in EGFR-mutant NSCLC patients that develop resistance to osimertinib. This observation merits to be further evaluated in a prospective immunotherapy trial. © 2021, The Author(s).
ER -