Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China.
World J Gastroenterol. 2019 Jan 7;25(1):138-150. doi: 10.3748/wjg.v25.i1.138.
To evaluate the clinical properties of three subpopulations of circulating tumor cells (CTCs) undergoing epithelial-mesenchymal transition (EMT) in pancreatic ductal adenocarcinoma (PDAC) patients.
We identified CTCs for expression of the epithelial cell marker cytokeratin or epithelial cell adhesion molecule (EpCAM) (E-CTC), the mesenchymal cell markers vimentin and twist (M-CTC), or both (E/M-CTC) using the CanPatrol system. Between July 2014 and July 2016, 107 patients with PDAC were enrolled for CTC evaluation. CTC enumeration and classification were correlated with patient clinicopathological features and outcomes.
CTCs were detected in 78.5% of PDAC patients. The number of total CTCs ranged from 0 to 26 across all 107 patients, with a median value of six. CTC status correlated with lymph node metastasis, TNM stage, distant metastasis, blood lymphocyte counts, and neutrophil-to-lymphocyte ratio (NLR). Kaplan-Meier survival analysis showed that patients with ≥ 6 total CTCs had significantly decreased overall survival and progression-free survival compared with patients with < 6 total CTCs. The presence of M-CTCs was positively correlated with TNM stage ( < 0.01) and distant metastasis ( < 0.01). Additionally, lymphocyte counts and NLR in patients without CTCs were significantly different from those in patients testing positive for each CTC subpopulation ( < 0.01).
Classifying CTCs by EMT markers helps to identify the more aggressive CTC subpopulations and provides useful evidence for determining a suitable clinical approach.
评估胰腺导管腺癌(PDAC)患者中经历上皮-间充质转化(EMT)的循环肿瘤细胞(CTC)的三个亚群的临床特征。
我们使用 CanPatrol 系统鉴定表达上皮细胞标志物细胞角蛋白或上皮细胞黏附分子(EpCAM)(E-CTC)、间充质细胞标志物波形蛋白和 twist(M-CTC)或两者(E/M-CTC)的 CTC。2014 年 7 月至 2016 年 7 月,纳入 107 例 PDAC 患者进行 CTC 评估。CTC 计数和分类与患者的临床病理特征和结局相关。
78.5%的 PDAC 患者检测到 CTCs。107 例患者的总 CTC 数从 0 到 26 不等,中位数为 6。CTC 状态与淋巴结转移、TNM 分期、远处转移、血液淋巴细胞计数和中性粒细胞与淋巴细胞比值(NLR)相关。Kaplan-Meier 生存分析显示,总 CTC 数≥6 的患者总生存期和无进展生存期明显低于总 CTC 数<6 的患者。M-CTC 的存在与 TNM 分期(<0.01)和远处转移(<0.01)呈正相关。此外,无 CTCs 患者的淋巴细胞计数和 NLR 与每个 CTC 亚群阳性患者的差异有统计学意义(<0.01)。
通过 EMT 标志物对 CTC 进行分类有助于识别侵袭性更强的 CTC 亚群,并为确定合适的临床治疗方法提供有价值的证据。