Reliable biomarkers in patients (pts) with pancreatic cancer (PC) are highly warranted. The aim of this prospective-retrospective biomarker study was to investigate the clinical value of cell-free DNA (cfDNA) in pts with PC.
A total of 377 consecutive pts with histologically confirmed PC and 94 healthy controls were included. Total cfDNA levels were determined by a direct fluorescent assay in EDTA plasma samples obtained before operation (stage I and II) or start of palliative chemotherapy (stage III and IV). Serum CA19-9 (IMMULITE 2000, Siemens), hyaluronic acid (HA) (ELISA, R&D), interleukin-6 (IL-6) (ELISA, R&D) and YKL-40 (ELISA, Quidel) were measured. The main outcome was association of cfDNA with overall survival (OS) for pts with PC. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards regression.
Pts with PC had significantly higher level of plasma cfDNA (median (range): 1.15 [0.45, 4.94] ng/uL) compared with healthy subjects (0.52 [0.48, 0.57] ng/uL, ROC analysis AUC 0.89). The level of plasma cfDNA was significantly increased with advanced stage, presence of liver metastases and worse Performance Status (PS). When analyzed as a continuous parameter, cfDNA higher than median of 1.15 ng/uL alone was associated with reduced OS (HR = 1.40, 95% CI 1.13-1.72, P = 0.002) in univariate analyses along with age >50, worse PS, higher stage, presence of liver metastases, and log2-transformed serum levels of CA19-9, HA, IL-6 and YKL-40. In multivariate analysis, plasma cfDNA (median and 75% quartile as cutoff) was not statistically significantly associated with OS, but CA19-9 and IL-6 along with higher age, PS, stage and presence of liver metastases were associated with shorter OS.
Plasma cfDNA concentrations measured with a simple assay was higher in PC patients than in healthy individuals. High plasma cfDNA levels were associated with a short OS. Adjusted for a number of known prognostic parameters cfDNA was not statistically significantly associated with OS.
Clinical trial identification
Legal entity responsible for the study
Julia Sidenius Johansen.
Has not received any funding.
All authors have declared no conflicts of interest.