PD-007 CXCR4, CXCR7 and CXCL12 expression is not a prognostic predictive factor in patients with resected pancreatic cancer - results from the CONKO-001 trial

Abstract

Introduction: Pancreatic cancer is a disease with a dismal prognosis. Several biomarkers have been tested in heterogeneous patient groups. Our aim was to evaluate the expression of the chemokine receptors CXCR4, CXCR7 and their common ligand CXCL12 as predictive and/or prognostic factors of adjuvant chemotherapy with gemcitabine and to evaluate their association with type of metastases. Methods: CXCR4, CXCR7 and CXCL12 expression was analyzed in resected pancreatic cancer tissues by immunohistochemistry from 160 of 368 patients enrolled in the CONKO‐001 trial, which established gemcitabine as a standard of adjuvant therapy. The correlation of CXCR4/CXCR7/CXCL12 expression with survival was analyzed by fitting a Cox proportional hazards model with respect to the type of recurrence (local and/or distant) and the location of metastases. Kaplan‐Meier analyses for median disease‐free survival (DFS) and overall survival (OS) were performed in dependence on CXCR4, CXCR7, and CXCL12 expression. Results: CXCR4 was positive in 128/160 patients (80%), CXCR7 in 63/157 (40%) and CXCL12 in 110/158 patients (70%). There was no correlation of CXCR4/CXCR7/CXCL12 expression with type of recurrence (local and/or distant) or the location of metastases. Expression of CXCR4 (median DFS low vs. high 10.3 vs 11.0, p = 0.31), CXCR7 (median DFS low vs. high 11.2 vs 9.5, p = 0.87), and CXCL12 (median DFS low vs. high 9.0 vs 11.8, p = 0.89) did not show a difference in DFS and OS neither in the overall study population nor in the stratified analysis according to treatment arm. The multivariable analysis including covariates treatment arm, resection status, grading, Karnofsky performance status, nodal involvement, tumor stage, and expression of CXCR4 did not show a significant correlation with disease‐free survival (HR 0.92, CI 0.62‐1.36). Conclusion: Our data show neither a predictive nor a prognostic role of CXCR4, CXCR7, and CXCL12 in patients with pancreatic cancer. In contrast to previously reported studies, our results do not confirm an association between the expression of CXCR4, CXCR7, and their common ligand CXCL12 with the type of recurrence. Nevertheless, further studies are needed to validate their role in predicting recurrence patterns.