Abstract
Liquid biopsy may assist in the management of cancer patients, which can be particularly applicable in pancreatic ductal adenocarcinoma (PDAC). In this study, we investigated the utility of circulating cell-free DNA (cfDNA)-based markers as prognostic tools in metastatic PDAC. Plasma was obtained from 61 metastatic PDAC patients, and cfDNA levels and fragmentation were determined. BEAMing technique was used for quantitative determination of RAS mutation allele fraction (MAF) in cfDNA. We found that the prognosis was more accurately predicted by RAS mutation detection in plasma than in tissue. RAS mutation status in plasma was a strong independent prognostic factor for both overall survival (OS) and progression-free survival (PFS). Moreover, RAS MAF in cfDNA was also an independent risk factor for poor OS, and was strongly associated with primary tumours in the body/tail of the pancreas and liver metastases. Higher cfDNA levels and fragmentation were also associated with poorer OS and shorter PFS, body/tail tumors, and hepatic metastases, whereas cfDNA fragmentation positively correlated with RAS MAF. Remarkably, the combination of CA19-9 with MAF, cfDNA levels and fragmentation improved the prognostic stratification of patients. Furthermore, dynamics of RAS MAF better correlated with patients’ outcome than standard CA19-9 marker. In conclusion, our study supports the use of cfDNA-based liquid biopsy markers as clinical tools for the non-invasive prognosis and monitoring of metastatic PDAC patients.
Highlights
Pancreatic cancer is the fourth leading cause of cancer death in Europe in both males and females, with the lowest survival rate of all cancers and responsible for over 95,000 deaths every year [1,2].While, the death rates of the most common cancers have mostly declined over the past decades, the mortality rate of pancreatic cancer remains flat or slightly increases over time [3]
For the analysis of RAS mutational status, primary tumor tissue was available in 70.5% (43/61) of patients
Our results reveal that circulating KRAS mutation allele fraction (MAF) in cell-free DNA (cfDNA) predicted survival in metastatic pancreatic ductal adenocarcinoma (PDAC)
Summary
Pancreatic cancer is the fourth leading cause of cancer death in Europe in both males and females, with the lowest survival rate of all cancers and responsible for over 95,000 deaths every year [1,2]. The death rates of the most common cancers have mostly declined over the past decades, the mortality rate of pancreatic cancer remains flat or slightly increases over time [3]. Pancreatic ductal adenocarcinoma (PDAC) represents more than 90% of all pancreatic cancer. Cancers 2020, 12, 1754 and the vast majority of deaths are associated with this tumor type. 60–70% of patients have a primary tumor, located in the head of pancreas, while 20% and 25% are located in the body, and tail, respectively. PDAC metastasizes mainly to liver, abdomen and lungs [4]
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