Surgery is the only potentially curative option for patients with pancreatic ductal adenocarcinoma (PDAC), but metastatic relapse remains common. We hypothesized that the expression levels of inflammatory cytokines could predict recurrence of PDAC, thus allowing to select patients who most likely could benefit from surgical resection.
We prospectively collected plasma at diagnosis from two-hundred eighty-seven patients with pancreatic resectable neoplasms. The expression levels of 23 cytokines were measured in ninety patients with PDAC by using a multiplex analyte profiling assay.
Levels higher than cutoff identified of the TH2 cytokines interleukin (IL)4, IL5, IL6, of macrophage inflammatory protein (MIP)1a, granulocyte-macrophage colony-stimulating factor (GM-CSF), and monocyte chemoattractant protein (MCP)1, and of IL17a, IFN-γ- induced protein (IP)10, and IL1b were significantly associated with a shorter median OS. In particular, levels of IL4 and IP10 higher than cutoff identified, and level of TH1 cytokines TNFa and INFg, and of IL9 and IL1Ra lower than cutoff identified were significantly associated with a shorter DFS. In the multivariate analysis, high IP10 was confirmed as negatively associated with OS (HR = 3.097, P=0.014) and IL4 and TNFa remain negatively (HR = 2.75, P=0.002) and positively (HR = 0.224, P=0.049) associated with DFS, respectively. Simultaneous expression of low IL4 and high TNFa identified patients with best prognosis (HR = 0.313, P
We demonstrated that, among a series of cytokines, IL4 is the most significant independent prognostic factor for DFS in resectable PDAC patients, and it could be useful to select patients with high risk of early recurrence who may avoid an unnecessary resection.
Clinical trial identification
Legal entity responsible for the study
University of Verona
Associazione Italiana per la Ricerca sul Cancro (AIRC)
All authors have declared no conflicts of interest.