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Quantification of BIM mRNA in circulating tumor cells of osimertinib-treated patients with EGFR mutation-positive lung cancer

Respiratory Investigation, ISSN: 2212-5345, Vol: 59, Issue: 4, Page: 535-544
2021
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Article Description

The response rate for osimertinib is high among patients with untreated epidermal growth factor receptor ( EGFR ) mutation-positive non-small cell lung cancer (NSCLC). However, there exist no biomarkers to predict the efficacy of the same. This study investigated whether BIM-γ mRNA expression in circulating tumor cells (CTCs) predicts poor outcomes for osimertinib treatment in patients with EGFR mutation-positive NSCLC. Patients with advanced EGFR-tyrosine kinase inhibitor-untreated NSCLC or post-operative recurrence with EGFR -sensitive mutations (exon 19 deletion or L858R mutation) were included. Informed consent was obtained from all participants. The candidate biomarker BIM-γ was measured in CTCs after blood collection (10 mL of whole blood) at baseline. CTCs were collected with the ClearCell FX system, and quantitative real-time PCR was performed. Relative expression of BIM-γ mRNA from CTCs, as normalized to the reference gene (GAPDH mRNA), was calculated using the KCL22 cell line for calibration. We enrolled 30 EGFR mutation-positive NSCLC patients treated with osimertinib during the period from April 2018 through December 2019. All the patients had an EGFR mutation at the primary site: exon 19 deletion in 15 cases and L858R in 15 cases. Median CTC count at baseline was 12 (range 3–127)/7.5 mL, and median BIM-γ mRNA expression was 0.073 (range 0–1.37). Furthermore, the response rate to osimertinib was worse in patients with high than in those with low BIM-γ mRNA expression (n = 15 each) (26.6% vs. 73.3%, respectively; p  = 0.011). Progression-free survival did not significantly differ between groups ( p  = 0.13). BIM-γ mRNA overexpression in CTCs from EGFR mutation-positive NSCLC patients is a potential a biomarker for poor response to osimertinib. UMIN:00032055.

Bibliographic Details

Isobe, Kazutoshi; Yoshizawa, Takahiro; Sekiya, Muneyuki; Miyoshi, Shion; Nakamura, Yasuhiko; Urabe, Naohisa; Isshiki, Takuma; Sakamoto, Susumu; Takai, Yujiro; Tomida, Taichiro; Adachi-Akahane, Satomi; Iyoda, Akira; Homma, Sakae; Kishi, Kazuma

Elsevier BV

Medicine

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