Pancreatic cancer is an aggressive, solid tumor, with a grave prognosis. Despite surgical treatment in patients with pancreatic cancer, the rate of recurrence is high. In addition, although tumor biomarkers are frequently used to confirm advanced pancreatic cancer, this is not accurate and the biomarkers currently used cannot indicate prognosis. This study sought to evaluate circulating tumor DNA as a tumor biomarker to prognosticate pancreatic cancer. Patients with advanced pancreatic cancer and liver metastasis (N = 104) were included, and blood samples were collected from all patients. The mutant allele frequency was measured using amplicon-based deep sequencing on a cell-free DNA panel covering 14 genes with > 240 hot spots. In patients with advanced pancreatic cancer, 50% (N = 52) had detectable ctDNA levels, with TP53 (45%, N = 47) and KRAS (42.3%, N = 44) mutations the most common. Patients with detectable circulating tumor DNA levels also had significantly worse overall survival and progression free survival than ctDNA negative patients (8.4 vs 16 months, P<0.0001 for overall survival; 3.2 vs 7.9 months, P<0.0001 for progression-free survival). In a multivariate analysis, ctDNA status was independently associated with overall survival and progression-free survival (HR = 3.1, 95%CI = 1.9–5.0, P<0.0001; HR 2.6, 95%CI = 1.7–4.0, P<0.0001, respectively). Moreover, circulating tumor DNA significantly correlated with a higher number of liver metastases, the presence of lung and/or peritoneal metastases, tumor burden, and higher carbohydrate antigen 19–9 levels. This study supports the use of circulating tumor DNA as an independent prognostic marker for advanced pancreatic cancer.

胰腺癌是一种侵袭性实体瘤，预后严重。尽管对胰腺癌患者进行了手术治疗，但其复发率很高。另外，尽管经常使用肿瘤生物标记物来确认晚期胰腺癌，但这并不准确，并且当前使用的生物标记物不能指示预后。这项研究试图评估循环肿瘤DNA作为预后胰腺癌的肿瘤生物标志物。包括晚期胰腺癌和肝转移（N = 104）的患者，并从所有患者中收集血液样本。使用基于扩增子的深度测序在无细胞DNA面板上测量突变的等位基因频率，该面板包含14个具有> 240个热点的基因。在晚期胰腺癌患者中，有50％（N = 52）的ctDNA水平可检测到，TP53（45％，N = 47）和KRAS（42.3％，N = 44）突变最为常见。与ctDNA阴性的患者相比，可检测到的循环肿瘤DNA水平的患者的总生存期和无进展生存期也明显较差（8.4 vs 16个月，总生存期P <0.0001； 3.2 vs 7.9个月，无进展生存期P <0.0001）。在多变量分析中，ctDNA的状态与总体生存和无进展生存独立相关（HR = 3.1，95％CI = 1.9–5.0，P <0.0001； HR 2.6，95％CI = 1.7–4.0，P <0.0001，分别）。此外，循环中的肿瘤DNA与更高数量的肝转移，肺和/或腹膜转移的存在，肿瘤负担以及更高的19-19糖类抗原水平显着相关。