Department of Respiratory Medicine, Toho University School of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, 143-8541, Japan.
Department of Respiratory Medicine, Toho University School of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, 143-8541, Japan.
Respir Investig. 2021 Jul;59(4):535-544. doi: 10.1016/j.resinv.2021.03.010. Epub 2021 Apr 29.
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.
对于未经治疗的表皮生长因子受体（EGFR）突变阳性非小细胞肺癌（NSCLC）患者，奥希替尼的缓解率很高。然而，目前还没有预测其疗效的生物标志物。本研究旨在探讨循环肿瘤细胞（CTC）中 BIM-γ mRNA 的表达是否可预测 EGFR 突变阳性 NSCLC 患者奥希替尼治疗的不良预后。
纳入接受过晚期 EGFR 酪氨酸激酶抑制剂治疗或术后复发且存在 EGFR 敏感突变（外显子 19 缺失或 L858R 突变）的 NSCLC 患者。所有参与者均获得知情同意。在基线时采集 10ml 全血后，用 ClearCell FX 系统采集 CTC 并进行实时定量 PCR。用 KCL22 细胞系进行校准，计算 CTC 中 BIM-γ mRNA 的相对表达量（相对于参考基因 GAPDH mRNA）。
本研究纳入了 2018 年 4 月至 2019 年 12 月期间接受奥希替尼治疗的 30 例 EGFR 突变阳性 NSCLC 患者。所有患者的原发部位均存在 EGFR 突变：15 例为外显子 19 缺失，15 例为 L858R。基线时 CTC 计数中位数为 12（范围 3-127）/7.5ml，中位 BIM-γ mRNA 表达量为 0.073（范围 0-1.37）。此外，高 BIM-γ mRNA 表达患者（n=15）的奥希替尼治疗缓解率差于低 BIM-γ mRNA 表达患者（n=15）（分别为 26.6%和 73.3%；p=0.011）。两组患者的无进展生存期无显著差异（p=0.13）。
EGFR 突变阳性 NSCLC 患者 CTC 中 BIM-γ mRNA 的过度表达可能是对奥希替尼治疗反应不良的潜在生物标志物。
UMIN:00032055。
