Department of Pathology, Technische Universität Dresden, Dresden, Germany.
Oncology. 2012;82(1):3-10. doi: 10.1159/000335479. Epub 2012 Jan 20.
The aim of this study was to develop an immunomagnetic/real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay and assess its clinical value for the molecular detection of circulating tumor cells (CTCs) in peripheral blood of pancreatic cancer patients.
The presence of CTCs was evaluated in 34 pancreatic cancer patients before systemic therapy and in 40 healthy controls, through immunomagnetic enrichment, using the antibodies BM7 and VU1D9 [targeting mucin 1 and epithelial cell adhesion molecule (EpCAM), respectively], followed by real-time RT-PCR analysis of the genes KRT19, MUC1, EPCAM, CEACAM5 and BIRC5.
The developed assay showed high specificity, as none of the healthy controls were found to be positive for the multimarker gene panel. CTCs were detected in 47.1% of the pancreatic cancer patients before the beginning of systemic treatment. Shorter median progression-free survival (PFS) was observed for patients who had at least one detectable tumor-associated transcript, compared with patients who were CTC negative. Median PFS time was 66.0 days [95% confidence interval (CI) 44.8-87.2] for patients with baseline CTC positivity and 138.0 days (95% CI 124.1-151.9) for CTC-negative patients (p = 0.01, log-rank test).
Our results suggest that in addition to the current prognostic methods, CTC analysis represents a potential complementary tool for prediction of outcome in pancreatic cancer patients.
本研究旨在开发一种免疫磁珠/实时逆转录聚合酶链反应(RT-PCR)检测方法,并评估其用于检测胰腺癌患者外周血循环肿瘤细胞(CTC)的临床价值。
通过免疫磁珠富集,使用针对黏蛋白 1 和上皮细胞黏附分子(EpCAM)的抗体 BM7 和 VU1D9,评估 34 例接受系统治疗前的胰腺癌患者和 40 例健康对照者中 CTC 的存在情况,随后对 KRT19、MUC1、EPCAM、CEACAM5 和 BIRC5 基因进行实时 RT-PCR 分析。
所开发的检测方法显示出高特异性,因为在健康对照组中均未发现多标记基因组合呈阳性。在开始系统治疗前,47.1%的胰腺癌患者检测到 CTC。与 CTC 阴性患者相比,至少有一种检测到的肿瘤相关转录本的患者中位无进展生存期(PFS)较短。基线 CTC 阳性患者的中位 PFS 时间为 66.0 天(95%CI:44.8-87.2),而 CTC 阴性患者的中位 PFS 时间为 138.0 天(95%CI:124.1-151.9)(p=0.01,对数秩检验)。
我们的结果表明,除了目前的预后方法外,CTC 分析可能是预测胰腺癌患者预后的一种潜在互补工具。