State Key Laboratory of Molecular Oncology, Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of VIP Medical Services & Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
J Cancer Res Clin Oncol. 2022 May;148(5):1137-1146. doi: 10.1007/s00432-021-03681-9. Epub 2021 Jul 13.
To analyze the clinical relevance of heterogeneous phenotypes of peripheral circulating tumor cells (CTCs) in non-small cell lung cancer (NSCLC).
CTCs in 5 mL venous blood were enriched using the Canpatrol™ CTC technique in 82 NSCLC patients. And then, CTCs were subjected to RNA in situ hybridization with a combination of epithelial (EpCAM and CK8/18/19) and mesenchymal (vimentin and TWIST1) markers.
According to the fluorescent dots, CTCs were classified into three groups, including epithelial CTCs (E-CTC), hybrid epithelial/mesenchymal phenotypes (E/M-CTCs) and mesenchymal CTCs (M-CTCs). In 82 NSCLC cohort, only 2 patients didn't detect CTCs, the overall CTCs detection rate was 97.5% (80/82). For 60 treatment naïve NSCLC, only one patient didn't detect CTCs. The median number of total CTCs, hybrid E/M phenotype CTCs, E-CTCs and M-CTCs per 5 mL blood was 22 (range 1-90), 13 (range 0-83), 1 (range 0-17 and 0-47), respectively. Hybrid E/M CTCs, especially the e = m-CTCs, significantly differed between patients with and without distant metastasis. M-CTCs in advanced NSCLC patients were significantly more than the numbers observed in early stage patients. Patients with pure hybrid E/M-CTCs showed a lower proportion in distant metastasis positive cohort compared to negative ones (7% vs 22%), while patients with E + E/M CTCs (20% vs 9%) and E/M + M CTCs (33% vs 20%) showed a higher proportion. CTCs dynamic changes after treatment in 12 advanced NSCLC patients suggested that hybrid E/M-CTCs were related to the primary tumor size at baseline, while M-CTCs may suggest the progression of NSCLC.
We concluded that E-CTCs with a hybrid E/M phenotype are associated to metastasis in therapy-naïve NSCLC patients.
分析非小细胞肺癌（NSCLC）外周循环肿瘤细胞（CTC）异质性表型的临床相关性。
采用 Canpatrol™ CTC 技术从 82 例 NSCLC 患者的 5mL 静脉血中富集 CTC，并用上皮（EpCAM 和 CK8/18/19）和间充质（波形蛋白和 TWIST1）标志物的组合对 CTC 进行 RNA 原位杂交。
根据荧光斑点，将 CTC 分为三组，包括上皮 CTC（E-CTC）、上皮/间充质混合表型（E/M-CTCs）和间充质 CTC（M-CTC）。在 82 例 NSCLC 队列中，只有 2 例患者未检测到 CTC，总 CTC 检测率为 97.5%（80/82）。在 60 例初治 NSCLC 患者中，仅 1 例患者未检测到 CTC。每 5mL 血液中总 CTC、混合 E/M 表型 CTC、E-CTC 和 M-CTC 的中位数分别为 22（范围 1-90）、13（范围 0-83）、1（范围 0-17 和 0-47）。混合 E/M CTC，特别是 e = m-CTCs，在有和无远处转移的患者之间有显著差异。晚期 NSCLC 患者的 M-CTCs 明显多于早期患者。纯混合 E/M-CTCs 患者在远处转移阳性队列中的比例低于阴性队列（7%比 22%），而 E + E/M CTCs（20%比 9%）和 E/M + M CTCs（33%比 20%）的比例较高。12 例晚期 NSCLC 患者治疗后 CTC 的动态变化表明，混合 E/M-CTCs 与基线时的原发肿瘤大小有关，而 M-CTCs 可能提示 NSCLC 的进展。
我们得出结论，E-CTC 具有混合 E/M 表型与治疗初治 NSCLC 患者的转移有关。
