Zhao Xudong, Ma Yongsu, Dong Xiu, Zhang Zhengkui, Tian Xiaodong, Zhao Xiaohang, Yang Yinmo
Department of General Surgery, Peking University First Hospital, Beijing, China.
State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Hepatobiliary Surg Nutr. 2021 Dec;10(6):796-810. doi: 10.21037/hbsn-20-383.
The clinical value of heterogeneous sub-populations of circulating tumor cells (CTCs) in pancreatic ductal adenocarcinoma (PDAC) remains unclear.
Peripheral blood samples were obtained from 67 PDAC patients. CTCs were isolated by employing CD45 negative enrichment technique and further characterized for epithelial to mesenchymal transition (EMT) or human equilibrative nucleoside transporter-1 (hENT-1). The relationships between CTCs sub-phenotypes with clinicopathological factors or post-operative recurrence in PDAC patients were analyzed.
EMT related CTCs could be isolated and identified from the 81% of patients (54/67), and both the total count (median: 5 17/mL, P<0.0001) and M-CTC percentage (median: 0.2 0.345, P=0.0244) of CTCs could differentiate local/regional with metastatic disease. Multivariate analysis showed that both AJCC stage (P=0.025) and M-CTC percentage (P=0.001) were independent prognostic indicators of recurrence free survival (RFS) in resected patients. Moreover, Kaplan-Meier survival analysis showed that M-CTC after 2 courses of chemotherapy was significantly associated with inferior RFS (49.5 weeks undefined, P=0.0288). No significant correlation in hENT-1 expression was found between CTCs and matched tumor tissues, and further multivariate analysis suggested hENT-1 expression in CTCs as independent prognostic factor for RFS (P=0.016). Patients with low hENT-1 expression in CTCs had decreased RFS (32 weeks undefined, P=0.0337).
CTCs could be the promising diagnostic biomarkers in PDAC patients, and phenotypic profiling of CTCs based on EMT or hENT-1 could help establish novel prognostic biomarkers in resected patients undergoing adjuvant gemcitabine-based chemotherapy.
Circulating tumor cells (CTCs); Pancreatic ductal adenocarcinoma (PDAC); Epithelial to mesenchymal transition (EMT); human equilibrative nucleoside transporter-1 (hENT-1).
循环肿瘤细胞（CTC）的异质性亚群在胰腺导管腺癌（PDAC）中的临床价值仍不清楚。
从67例PDAC患者中采集外周血样本。采用CD45阴性富集技术分离CTC，并进一步对其上皮-间质转化（EMT）或人平衡核苷转运体-1（hENT-1）进行特征分析。分析PDAC患者CTC亚表型与临床病理因素或术后复发之间的关系。
81%（54/67）的患者可分离并鉴定出与EMT相关的CTC，CTC的总数（中位数：5.17/mL，P<0.0001）和M-CTC百分比（中位数：0.2±0.345，P=0.0244）均可区分局部/区域疾病与转移性疾病。多因素分析显示，AJCC分期（P=0.025）和M-CTC百分比（P=0.001）均为切除患者无复发生存期（RFS）的独立预后指标。此外，Kaplan-Meier生存分析显示，2个疗程化疗后的M-CTC与较差的RFS显著相关（49.5周对未定义，P=0.0288）。在CTC与匹配的肿瘤组织之间未发现hENT-1表达有显著相关性，进一步的多因素分析表明，CTC中的hENT-1表达是RFS的独立预后因素（P=0.016）。CTC中hENT-1表达低的患者RFS降低（32周对未定义，P=0.0337）。
CTC可能是PDAC患者有前景的诊断生物标志物，基于EMT或hENT-1的CTC表型分析有助于在接受基于吉西他滨辅助化疗的切除患者中建立新的预后生物标志物。
循环肿瘤细胞（CTC）；胰腺导管腺癌（PDAC）；上皮-间质转化（EMT）；人平衡核苷转运体-1（hENT-1）
