Kim In Ae, Hur Jae Young, Kim Hee Joung, Kim Wan Seop, Lee Kye Young
Precision Medicine Lung Cancer Center, Konkuk University Medical Center, Seoul, Republic of Korea.
Department of Pathology, Konkuk University School of Medicine, Seoul, Republic of Korea.
Transl Lung Cancer Res. 2023 Jul 31;12(7):1425-1435. doi: 10.21037/tlcr-22-892. Epub 2023 Jun 19.
In our previous study, epidermal growth factor receptor () genotyping using extracellular vesicles (EV)-derived DNA isolated from bronchoalveolar lavage fluid (BALF) was proven to be highly concordant with conventional tissue-based genotyping and its turn-around-time (TAT) was only 1-2 days. On this background, we prospectively validated the performance of EV-based BALF liquid biopsy for genotyping in the real practice of advanced non-small cell lung cancer (NSCLC) patients.
After screening 120 newly diagnosed stage III-IV NSCLC patients, 51 cases were detected as -mutated by EV-based BALF genotyping and 40 patients were enrolled for gefitinib treatment. BALF EV were isolated by ultracentrifuge method and genotyping was performed with PCR-based PNA-clamping assisted fluorescence melting curve analysis. The objective response rate, progression-free survival (PFS), TAT, time to treatment initiation (TTI), and concordance rate were analyzed with clinical parameters.
There was only one false positive case among the 120 screened patients and the overall concordance rate between tissue biopsy and EV-based BALF liquid biopsy was 99.2% including the subtype of mutations. TAT for EV-based BALF genotyping was 1.9±1.1 days, while tissue-based TAT was 12.1±7.2 days (P<0.001). genotyping was determined even before obtaining histopathologic report in most cases. TTI in BALF genotyping was faster than tissue genotyping (7.8±6.5 . 13.8±12.9 days). Therapeutic outcomes of response rate and PFS were almost similar to tissue-based results.
We demonstrated, for the first time, that EV-based BALF liquid biopsy should be an excellent platform for expeditious genotyping and rapid therapeutic intervention even before obtaining the result of histopathology in advanced NSCLC patients.
在我们之前的研究中，使用从支气管肺泡灌洗液（BALF）中分离的细胞外囊泡（EV）衍生DNA进行表皮生长因子受体（EGFR）基因分型，被证明与传统的基于组织的基因分型高度一致，其周转时间（TAT）仅为1 - 2天。在此背景下，我们前瞻性地验证了基于EV的BALF液体活检在晚期非小细胞肺癌（NSCLC）患者实际临床中的EGFR基因分型性能。
在筛选120例新诊断的III - IV期NSCLC患者后，51例通过基于EV的BALF EGFR基因分型检测为EGFR突变，40例患者接受吉非替尼治疗。通过超速离心法分离BALF EV，并采用基于PCR的肽核酸钳夹辅助荧光熔解曲线分析进行EGFR基因分型。将客观缓解率、无进展生存期（PFS）、TAT、治疗开始时间（TTI）和符合率与临床参数进行分析。
在120例筛选患者中仅有1例假阳性病例，组织活检与基于EV的BALF液体活检之间的总体符合率为99.2%，包括EGFR突变亚型。基于EV的BALF EGFR基因分型的TAT为1.9±1.1天，而基于组织的TAT为12.1±7.2天（P<0.001）。在大多数情况下，甚至在获得组织病理学报告之前就确定了EGFR基因分型。BALF EGFR基因分型的TTI比组织基因分型更快（7.8±6.5对13.8±12.9天）。缓解率和PFS的治疗结果与基于组织的结果几乎相似。
我们首次证明，基于EV的BALF液体活检即使在晚期NSCLC患者获得组织病理学结果之前，也应是快速EGFR基因分型和快速治疗干预的优秀平台。
