Piro Geny, Simionato Francesca, Carbone Carmine, Frizziero Melissa, Malleo Giuseppe, Zanini Silvia, Casolino Raffaella, Santoro Raffaela, Mina Maria Mihaela, Zecchetto Camilla, Merz Valeria, Scarpa Aldo, Bassi Claudio, Tortora Giampaolo, Melisi Davide
Digestive Molecular Clinical Oncology Research Unit, Department of Medicine, Università degli studi di Verona, Verona, Italy.
Laboratory of Oncology and Molecular Therapy, Department of Medicine, Università degli studi di Verona, Verona, Italy.
Oncoimmunology. 2017 Apr 28;6(9):e1322242. doi: 10.1080/2162402X.2017.1322242. eCollection 2017.
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 287 patients with pancreatic resectable neoplasms. The expression levels of 23 cytokines were measured in 90 patients with PDAC by using a multiplex analyte profiling assay. Levels higher than cutoff identified of the T2 cytokines interleukin (IL)4, IL5, IL6 of macrophage inflammatory protein (MIP)1α, granulocyte-macrophage colony-stimulating factor (GM-CSF), and monocyte chemoattractant protein (MCP)1, and of IL17α, IFNγ-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 T1 cytokines TNFα and INFγ, and of IL9 and IL1Rα 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, = 0.014) and IL4 and TNFα remain negatively (HR = 2.75, = 0.002) and positively (HR = 0.224, = 0.049) associated with DFS, respectively. Simultaneous expression of low IL4 and high TNFα identified patients with best prognosis (HR = 0.313, < 0.0001). In conclusion, 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.
手术是胰腺导管腺癌（PDAC）患者唯一可能治愈的选择，但转移性复发仍然很常见。我们假设炎性细胞因子的表达水平可以预测PDAC的复发，从而能够选择最有可能从手术切除中获益的患者。我们前瞻性地收集了287例可切除胰腺肿瘤患者诊断时的血浆。通过使用多重分析物谱分析测定法，在90例PDAC患者中测量了23种细胞因子的表达水平。巨噬细胞炎性蛋白（MIP）1α、粒细胞-巨噬细胞集落刺激因子（GM-CSF）、单核细胞趋化蛋白（MCP）1的T2细胞因子白细胞介素（IL）4、IL5、IL6，以及IL17α、干扰素γ诱导蛋白（IP）10和IL1b高于临界值的水平与较短的中位总生存期显著相关。特别是，高于临界值的IL4和IP10水平，以及低于临界值的T1细胞因子肿瘤坏死因子α（TNFα）和干扰素γ（INFγ），以及IL9和IL1Rα水平与较短的无病生存期显著相关。在多变量分析中，高IP10被确认为与总生存期呈负相关（风险比=3.097，P=0.014），而IL4和TNFα分别与无病生存期呈负相关（风险比=2.75，P=0.002）和正相关（风险比=0.224，P=0.049）。低IL4和高TNFα的同时表达确定了预后最佳的患者（风险比=0.313，P<0.0001）。总之，我们证明，在一系列细胞因子中，IL4是可切除PDAC患者无病生存期最重要的独立预后因素，它可能有助于选择有早期复发高风险的患者，这些患者可能避免不必要的切除。
