Department of Molecular Diagnostics, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), 12519Peking University Cancer Hospital and Institute, Beijing, China.
Department of Thoracic Surgery II, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), 12519Peking University Cancer Hospital and Institute, Beijing, China.
Int J Biol Markers. 2022 Dec;37(4):386-394. doi: 10.1177/03936155221099036. Epub 2022 Jul 6.
Non-invasive liquid biopsies of circulating tumor DNA (ctDNA) is a rapidly growing field in the research of non-small cell lung cancer (NSCLC). In this study, factors affecting the concordance of mutations in paired plasma and tissue and the detection rate of ctDNA in real-world Chinese patients with NSCLC were identified.
Peripheral blood and paired formalin-fixed paraffin-embedded tumor tissue samples from 125 NSCLC patients were collected and analyzed by sequencing 15 genes. Serological biomarkers were tested by immunoassay.
The overall concordance between tumor and plasma samples and the detection rate of somatic mutations in ctDNA was 69.2% and 78.4%, respectively. The concordance and detection rate raised with clinical stage were stage I: 14.3%, 14.3%; stage II: 53.3%, 60.0%; stage III: 71.4%, 78.1%; stage IV: 74.1%, 85.2%. With increased tumor diameter, the concordance and detection rate raised from 33.33% to 71.64% and 33.33% to 80.8%, respectively. For patients with partial response, stable disease, progressive disease, and who were treatment-naïve, the concordance and detection rates were 0.0%, 62.7%, 75.2, 73.6%, and 16.7%, 61.9%, 83.3%, 86.5%, respectively. Serological markers: CEA, CA125, NSE, and CYFRA21-1 were significantly higher for patients with detectable somatic alterations in ctDNA than in those who were ctDNA negative (17.08 ng/mL vs. 3.95 ng/mL, 21.63 U/mL vs. 18.27 U/mL, 17.68 U/mL vs. 14.14 U/mL, and 6.55 U/mL vs. 3.81 U/mL, respectively).
Advanced-stage, treatment naïve or poor therapy outcome, and large tumor size were associated with a high concordance and detection rate. Patients with detectable mutations in ctDNA had a higher level of carcinoembryonic antigen, CA125, NSE, and CYFRA21-1.
循环肿瘤 DNA（ctDNA）的非侵入性液体活检是研究非小细胞肺癌（NSCLC）的一个快速发展领域。本研究旨在确定影响配对血浆和组织突变一致性以及在中国 NSCLC 患者中检测 ctDNA 的检出率的因素。
收集 125 例 NSCLC 患者的外周血和配对福尔马林固定石蜡包埋肿瘤组织样本，通过测序 15 个基因进行分析。通过免疫测定法检测血清生物标志物。
肿瘤样本和血浆样本的总体一致性以及 ctDNA 体细胞突变的检出率分别为 69.2%和 78.4%。随着临床分期的增加，一致性和检出率也随之提高，Ⅰ期：14.3%、14.3%；Ⅱ期：53.3%、60.0%；Ⅲ期：71.4%、78.1%；Ⅳ期：74.1%、85.2%。随着肿瘤直径的增加，一致性和检出率分别从 33.33%提高至 71.64%和 33.33%提高至 80.8%。部分缓解、病情稳定、疾病进展和治疗初治患者的一致性和检出率分别为 0.0%、62.7%、75.2%和 73.6%以及 16.7%、61.9%、83.3%和 86.5%。血清标志物：CEA、CA125、NSE 和 CYFRA21-1 在 ctDNA 中可检测到体细胞改变的患者明显高于 ctDNA 阴性患者（17.08ng/ml 比 3.95ng/ml，21.63U/ml 比 18.27U/ml，17.68U/ml 比 14.14U/ml 和 6.55U/ml 比 3.81U/ml）。
晚期、初治或治疗效果不佳、肿瘤体积大与高一致性和高检出率相关。在 ctDNA 中可检测到突变的患者，CEA、CA125、NSE 和 CYFRA21-1 的水平更高。
