Plasma IFN-γ-inducible chemokines CXCL9 and CXCL10 correlate with survival and chemotherapeutic efficacy in advanced pancreatic ductal adenocarcinoma

Abstract

ObjectivesRecent studies have suggested that the CXCL9, 10, 11/CXCR3 axis is significant in immune regulation and therapeutic efficacy in human cancers; however, its role in pancreatic ductal adenocarcinoma (PDAC) remains unknown. This study serves to evaluate the prognostic prediction value of plasma IFN-γ-inducible chemokines, CXCL9 and CXCL10, in advanced PDAC. MethodsTwo hundred patients with advanced PDAC receiving palliative chemotherapy were retrospectively recruited. The association between Plasma CXCL9/CXCL10 levels and survival time was first analyzed in a test group of 110 patients and then confirmed in a validation group of 90 patients. ResultsHigh levels of CXCL9 and CXCL10 were significantly correlated with longer overall survival (OS) in advanced PDAC patients (314 vs. 136 days for CXCL9, P < 0.0001, and 374 vs. 163 days for CXCL10, P < 0.0001, respectively) in the test group, which was consistent with the results derived from the validation group. In addition, high levels of CXCL9 and CXCL10 were associated with longer time to progression (TTP) in patients receiving chemotherapy (100 vs. 60 days for CXCL9, P = 0.0021, and 104 vs. 67 days for CXCL10, P = 0.0057, respectively). Multivariate analyses confirmed that CXCL9 and CXCL10 were independent prognostic predictors for OS (hazard ratio [HR]: 0.452, P < 0.001 for CXCL9; and HR: 0.586, P = 0.007 for CXCL10, respectively) and TTP (HR: 0.656, P = 0.015 for CXCL9; and HR: 0.687, P = 0.040 for CXCL10, respectively). ConclusionsPlasma CXCL9 and CXCL10 can be used to predict survival of advanced PDAC patients receiving chemotherapy, allowing clinicians to potentially improve treatment outcomes by identifying candidates for aggressive therapy.