Jain Mark, Atayan David, Rakhmatullin Tagir, Dakhtler Tatiana, Inokenteva Victoria, Popov Pavel, Farmanov Aleksandr, Viborniy Mikhail, Gontareva Iuliia, Samokhodskaya Larisa, Egorov Vyacheslav
University Clinic, Lomonosov Moscow State University, 119992 Moscow, Russia.
Joint Stock Company "Ilyinsky Hospital", 143421 Moscow, Russia.
Int J Mol Sci. 2025 Sep 9;26(18):8763. doi: 10.3390/ijms26188763.
Cell-free DNA (cfDNA) analysis-based liquid biopsy is a rapidly emerging diagnostic and prognostic tool in pancreatic ductal adenocarcinoma (PDAC). point mutations are the main biomarkers used for the detection of tumor cfDNA. However, there is another less studied yet frequent genetic alteration in this gene, namely copy number gain (CNG). The aim of this study was to evaluate the diagnostic and prognostic potential of CNG analysis in plasma and bile of patients with PDAC using ddPCR. This study included healthy volunteers ( = 69), patients with PDAC ( = 94), and other pancreatic neoplasms (OPN) ( = 17). The sensitivity and specificity of CNG compared to the control group were 16% and 100% (AUC-ROC-0.580), and compared to the OPN group, 16% and 94% (AUC-ROC-0.554), respectively. Addition of KRAS point mutations to the analysis increased the sensitivity to 65% (AUC-ROC-0.824 and 0.801, respectively). Bile exhibited an equal CNG detection rate compared to plasma (20% vs. 16%). CNG was not associated with clinical parameters, except prognosis. The probability of survival was worse in patients with CNG (HR-3.54; 95% CI: 1.55-8.12; = 0.001). CNG in cfDNA might be a promising biomarker for both diagnostic and prognostic purposes in PDAC.
基于游离DNA（cfDNA）分析的液体活检是胰腺导管腺癌（PDAC）中一种迅速兴起的诊断和预后工具。点突变是用于检测肿瘤cfDNA的主要生物标志物。然而，该基因中存在另一种研究较少但常见的基因改变，即拷贝数增加（CNG）。本研究的目的是使用数字滴度PCR（ddPCR）评估CNG分析在PDAC患者血浆和胆汁中的诊断和预后潜力。本研究纳入了健康志愿者（n = 69）、PDAC患者（n = 94）和其他胰腺肿瘤（OPN）患者（n = 17）。与对照组相比，CNG的敏感性和特异性分别为16%和100%（AUC-ROC为0.580），与OPN组相比，分别为16%和94%（AUC-ROC为0.554）。在分析中加入KRAS点突变可将敏感性提高到65%（AUC-ROC分别为0.824和0.801）。与血浆相比胆汁表现出相同的CNG检测率（20%对16%）。除了预后外，CNG与临床参数无关。CNG患者的生存概率更差（HR = 3.54；95%CI：1.55 - 8.12；P = 0.001）。cfDNA中的CNG可能是PDAC诊断和预后的一种有前景的生物标志物。
