OncoTargets and Therapy (Jul 2016)
Potential predictive role of chemotherapy-induced changes of soluble CD40 ligand in untreated advanced pancreatic ductal adenocarcinoma
Abstract
Amalia Azzariti,1,* Oronzo Brunetti,2,* Letizia Porcelli,1 Giusi Graziano,3 Rosa Maria Iacobazzi,1 Michele Signorile,2 Aldo Scarpa,4 Vito Lorusso,2 Nicola Silvestris2 1Preclinical and Clinical Pharmacology Unit, 2Medical Oncology Unit, 3Scientific Direction, National Cancer Research Centre, Istituto Tumouri “Giovanni Paolo II”, Bari, 4ARC-NET Research Centre, University of Verona, Verona, Italy *These authors contributed equally to this work Abstract: Pancreas ductal adenocarcinoma lacks predictive biomarkers. CD40 is a member of the tumor necrosis factor superfamily. CD40–sCD40L interaction is considered to contribute to the promotion of tumor cell growth and angiogenesis. The aim of the present study was to investigate the role of serum sCD40L as a predictor in metastatic pancreatic cancer. We evaluated 27 consecutive pancreatic cancer patients treated with FOLFIRINOX (21 patients) or gemcitabine plus nab-paclitaxel combination (six patients). The sCD40L level was measured in serum by enzyme-linked immunosorbent assay at baseline, at first evaluation (all patients), and at time to progression (18 patients). The radiological response was evaluated according to the Response Evaluation Criteria in Solid Tumors, Version 1.1. The Wilcoxon signed-rank test was used to compare pre–post treatment sCD40L levels with respect to clinical response, while Pearson’s correlation coefficient was used for the correlation between sCD40L and CA19.9 pre- and post-treatment. The Kruskal–Wallis test was also conducted for further comparisons. We observed a statistically significant reduction in the sCD40L level after 3 months of treatment in patients with partial response (11,718.05±7,097.13 pg/mL vs 4,689.42±5,409.96 pg/mL; P<0.01). Conversely, in patients with progressive disease, the biomarker statistically increased in the same time (9,351.51±7,356.91 pg/mL vs 22,282.92±11,629.35 pg/mL; P<0.01). This trend of sCD40L was confirmed in 18 patients at time to progression after the first evaluation. No differences were recorded within the stable disease group. Moreover, there was a positive correlation between the sCD40L and CA19.9 pre–post treatment variation percentage (Pearson’s correlation coefficient =0.52; P<0.05). Our data suggest a possible predictive role of sCD40L in pancreatic cancer patients, similar to CA19.9. Keywords: pancreatic ductal adenocarcinoma, FOLFIRINOX, gemcitabine plus nab-paclitaxel, predictive factor, soluble CD40 ligand
