The association of KRAS mutation in circulating-tumor DNA and survival in patients with pancreatic cancer

Abstract

Circulating-tumor DNA (ctDNA) has been known to be released from tumor cells and investigated potential biomarkers for therapeutic responses. However, the role of ctDNA in pancreatic cancer has not been well studied. Here we selected KRAS mutation which has been known common over 95% of pancreatic ductal adenocarcinoma (PDA) and evaluated applicability as a prognostic marker through the quantitative analysis of ctDNA and KRAS mutation in the patients with PDA. Total of 147 PDA patients were enrolled in the study. The concentration and fraction of KRAS mutation were measured by KRAS screening multiplex droplet digital PCR kit (Biorad, USA) in plasma. Median of ctDNA concentration, KRAS mutant concentration and fractional abundance were 425 ng/mL, 0.11 copies/uL and 0.35 %, respectively. KRAS mutant concentration and fractional abundance showed the association with poor survival in OS (P =0.007 and P < .001). When we analyzed the receiver operating characteristic (ROC) curve to determine whether KRAS mutation in ctDNA have additive benefits with well-known tumor markers CA19-9, combined with KRAS mutation concentration or KRAS fractional abundance, the value of area under the curve (AUC) was significantly higher than the value calculated as CA19-9 alone. This study represents that KRAS mutant concentration and fractional abundance in ctDNA could be prognostic marker in pancreatic cancer.