PDF(Pubmed)
Abstract：
The key challenge of cell-free tumor DNA (cftDNA) analysis in pancreatic ductal adenocarcinoma (PDAC) is overcoming its low detection rate, which is mainly explained by the overall scarcity of this biomarker in plasma. Obstructive jaundice is a frequent event in PDAC, which enables bile collection as a part of routine treatment. The aim of this study was to evaluate the performance of KRAS-mutated cftDNA detection-based liquid biopsy of plasma and bile in patients with pancreatic neoplasms using digital droplet PCR. The study included healthy volunteers (n = 38), patients with PDAC (n = 95, of which 20 had obstructive jaundice) and other pancreatic neoplasms (OPN) (n = 18). The sensitivity and specificity compared to the control group were 61% and 100% (AUC-ROC-0.805), and compared to the OPN group, they were 61% and 94% (AUC-ROC-0.794), respectively. Bile exhibited higher cftDNA levels than plasma (248.6 [6.743; 1068] vs. 3.26 [0; 19.225] copies/mL) and a two-fold higher detection rate (p < 0.01). Plasma cftDNA levels were associated with distant metastases, tumor size, and CA 19-9 (p < 0.05). The probability of survival was worse in patients with higher levels of cftDNA in plasma (hazard ratio-2.4; 95% CI: 1.3-4.6; p = 0.005) but not in bile (p > 0.05). Bile is a promising alternative to plasma in patients with obstructive jaundice, at least for the diagnostic purposes of liquid biopsy.
摘要：
胰腺导管腺癌(PDAC)中无细胞肿瘤DNA(cftDNA)分析的关键挑战是克服其低检出率,这主要是由于血浆中这种生物标志物的整体稀缺性。阻塞性黄疸是PDAC中的常见事件，这使得胆汁收集成为常规治疗的一部分。这项研究的目的是使用数字液滴PCR评估胰腺肿瘤患者基于KRAS突变的cftDNA检测的血浆和胆汁液体活检的性能。这项研究包括健康志愿者(n=38)，PDAC（n=95，其中20例患有阻塞性黄疸）和其他胰腺肿瘤（OPN）（n=18）患者。与对照组相比，敏感性和特异性分别为61％和100％（AUC-ROC-0.805），与OPN组相比，它们分别为61%和94%(AUC-ROC-0.794)，分别。胆汁表现出比血浆更高的cftDNA水平（248.6[6.743;1068]vs.3.26[0;19.225]拷贝/mL）和两倍高的检出率（p<0.01）。血浆cftDNA水平与远处转移有关，肿瘤大小,和CA19-9(p<0.05)。血浆中cftDNA水平较高的患者的生存概率较差（风险比-2.4;95％CI：1.3-4.6;p=0.005），但胆汁中没有（p>0.05）。胆汁是阻塞性黄疸患者血浆的一种有希望的替代品，至少用于液体活检的诊断目的。
