Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea.
Anticancer Res. 2020 Jun;40(6):3435-3444. doi: 10.21873/anticanres.14329.
BACKGROUND/AIM: Although it has been suggested that circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) might be used in a complementary manner in lung cancer diagnosis, limited confirmatory data are available. In this prospective study, we evaluated the diagnostic performance of each assay separately and in combination.
From March 2018 to January 2019, patients with suspected primary lung cancer, who underwent routine lung cancer work-up and peripheral blood sampling, were prospectively enrolled in the study. Epithelial cell adhesion molecule and cytokeratin served as markers of CTCs. In terms of ctDNA analysis, single-nucleotide variants were evaluated via next-generation sequencing.
We analyzed 111 patients, including 99 with primary lung cancer and 12 with benign pulmonary disease. The median number of CTCs in 10 ml of blood was 3. The most frequently detected single nucleotide variants of ctDNA were TP53, CDKN2A, and EGFR. The diagnostic sensitivity of conventional tumor marker (combination of carcinoembryonic antigen/CYFRA 21-1/neuron-specific enolase) was 66.7%, while those of the ctDNA and CTC assays were 72.7% and 65.7%, respectively. The sensitivity of the CTC/ctDNA combination (95.0%) was significantly greater than those of the CTC (p<0.001), ctDNA (p<0.001), or conventional tumor marker (p<0.001) alone. Subgroup analysis revealed that the sensitivity of the combination assay was greater than those of the CTC or ctDNA assays alone, regardless of tumor stage or histopathology type.
The CTC/ctDNA combination assay enhanced the sensitivity of primary lung cancer diagnosis. The combination assay strategy may be clinically useful and could enhance the early detection of lung cancer (ClinicalTrials.gov number: NCT03479099).
背景/目的：虽然有研究表明循环肿瘤细胞（CTC）和循环肿瘤 DNA（ctDNA）可能在肺癌诊断中互补使用，但目前可用的确认性数据有限。在这项前瞻性研究中，我们分别评估了每种检测方法的诊断性能，并评估了它们的联合应用。
2018 年 3 月至 2019 年 1 月，我们前瞻性地招募了疑似患有原发性肺癌且接受常规肺癌检查和外周血采样的患者。上皮细胞黏附分子和细胞角蛋白被用作 CTC 的标志物。在 ctDNA 分析方面，通过下一代测序评估单核苷酸变体。
我们分析了 111 例患者，其中 99 例为原发性肺癌，12 例为良性肺部疾病。每 10ml 血液中的 CTC 中位数为 3。ctDNA 中最常检测到的单核苷酸变体为 TP53、CDKN2A 和 EGFR。常规肿瘤标志物（癌胚抗原/细胞角蛋白 21-1/神经元特异性烯醇化酶）的诊断敏感性为 66.7%，而 ctDNA 和 CTC 检测的诊断敏感性分别为 72.7%和 65.7%。CTC/ctDNA 联合检测的敏感性（95.0%）显著高于 CTC（p<0.001）、ctDNA（p<0.001）或常规肿瘤标志物（p<0.001）单项检测。亚组分析显示，无论肿瘤分期或组织病理学类型如何，联合检测的敏感性均高于 CTC 或 ctDNA 单项检测。
CTC/ctDNA 联合检测提高了原发性肺癌诊断的敏感性。联合检测策略可能具有临床应用价值，并能提高肺癌的早期检出率（ClinicalTrials.gov 编号：NCT03479099）。
