Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China.
J Clin Lab Anal. 2022 May;36(5):e24341. doi: 10.1002/jcla.24341. Epub 2022 Mar 25.
Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) is difficult due to the lack of effective screening tests. CA199, the standard biomarker for PDAC management, is not sufficiently reliable for early diagnosis. This prospective study aimed to evaluate whether circulating tumor cells (CTCs) could complement or perform better than CA199 in determining PDAC.
A total of 168 blood samples were collected from 80 patients with PDAC, 32 patients with acute pancreatitis, 22 patients with benign pancreatic masses, and 34 healthy donors. CTCs were detected by a novel system combining negative enrichment with immunostaining and fluorescence in situ hybridization (NE-imFISH). Next, ROC curves and AUC analyses were conducted to assess diagnostic abilities of CA199, CTCs, and the combination of the two biomarkers in PDAC.
CTCs were stained as CD45-/DAPI+/CEP8 ≥3. With 2 CTCs/3.2 ml as the cut-off value, the sensitivity/specificity of the CTC number was 0.76/0.94, which was comparable to that of CA199 (0.78/0.83; Delong test p = 0.3360). Improved performance was achieved through a logistic regression model integrating CA199 and CTC number (AUC = 0.95, AUC = 0.80, AUC = 0.85; Delong test p . < 0.0001 and p . = 0.0002). CTC subtype was inferior to CTC number as a diagnostic marker (AUC = 0.73; Delong test p . < 0.0001).
The dual-marker panel consisting of CA199 and CTC number can significantly improve upon the diagnostic performance of CA199 alone, highlighting the promising clinical utilization as an effective strategy for PDAC surveillance.
由于缺乏有效的筛查测试，胰腺导管腺癌 (PDAC) 的早期诊断较为困难。CA199 是 PDAC 管理的标准生物标志物，但用于早期诊断的可靠性不够。本前瞻性研究旨在评估循环肿瘤细胞 (CTC) 是否可以补充或优于 CA199 来确定 PDAC。
共收集 80 例 PDAC 患者、32 例急性胰腺炎患者、22 例良性胰腺肿块患者和 34 例健康供者的 168 份血样。CTC 采用结合阴性富集与免疫染色和荧光原位杂交（NE-imFISH）的新型系统进行检测。然后，通过 ROC 曲线和 AUC 分析评估 CA199、CTC 及其两种生物标志物组合在 PDAC 中的诊断能力。
CTC 被染色为 CD45-/DAPI+/CEP8≥3。以 2 CTCs/3.2 ml 为截断值，CTC 数的灵敏度/特异性为 0.76/0.94，与 CA199 相当（0.78/0.83；Delong 检验 p=0.3360）。通过整合 CA199 和 CTC 数的逻辑回归模型，性能得到了提高（AUC=0.95、AUC=0.80、AUC=0.85；Delong 检验 p<0.0001 和 p=0.0002）。CTC 亚型作为诊断标志物不如 CTC 数（AUC=0.73；Delong 检验 p<0.0001）。
由 CA199 和 CTC 数组成的双标志物组合可显著提高 CA199 单独检测的诊断性能，突出了其作为 PDAC 监测的有效策略的有前景的临床应用。
