Τίτλος:
Gene expression in circulating tumor cells reveals a dynamic role of EMT and PD-L1 during osimertinib treatment in NSCLC patients
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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).
Συγγραφείς:
Ntzifa, A.
Strati, A.
Kallergi, G.
Kotsakis, A.
Georgoulias, V.
Lianidou, E.
Περιοδικό:
Scientific Reports
Εκδότης:
Institute of Geographic Sciences and Natural Resources Research
Λέξεις-κλειδιά:
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
DOI:
10.1038/s41598-021-82068-9
