Abstract
PURPOSE: Kras mutation and abnormal immune status are associated with pancreatic cancer development and progression. In this study, we evaluated the Kras mutation status in circulating tumor DNA and circulating T cell subsets in a cohort of advanced pancreatic cancer patients. METHODS: Samples were retrospectively obtained from a series of 210 pathological advanced pancreatic cancer patients between 2012 and 2014. The Kras mutation status was detected in cell-free circulating tumor DNA (ctDNA) by ddPCR and circulating T cell subsets were analyzed by flow cytometry. RESULTS: Univariate analysis found that tumor node metastasis (TNM) stage, chemotherapy, circulating regulatory T cells, CA19-9 levels, CA125 levels, and Kras(G12D) and Kras(G12V) mutations were significantly related to overall survival in advanced pancreatic cancer patients. Multivariate analysis identified that TNM stage (P = .03, HR:1.422), Tregs (P = .004, HR:1.522), CA19-9 levels (P = .009, HR:1.488), Kras(G12D) mutation (P = .044, HR:1.353), and Kras(G12V) mutation (P = .001, HR:1.667) were independent prognostic markers. Furthermore, we found that Kras(G12V) mutation in ctDNA was correlated with high circulating proportion of Tregs, and patients with both Kras(G12V) mutation and high levels of Tregs were associated with extremely poor survival in advanced pancreatic cancer. CONCLUSION: Kras(G12V) mutation was associated with high circulating regulatory T cell levels, and both of them predicted worse prognosis in advanced pancreatic cancer patients.