Blank Susanne, Nienhüser Henrik, Dreikhausen Lena, Sisic Leila, Heger Ulrike, Ott Katja, Schmidt Thomas
Department of General, Visceral and Transplantation Surgery, University of Heidelberg, 69120 Heidelberg, Germany.
Romed Klinikum Rosenheim, 83022 Rosenheim, Germany.
Oncotarget. 2017 Jul 18;8(29):47518-47532. doi: 10.18632/oncotarget.17671.
Esophageal cancer is often marked by aggressive tumor growth and poor prognosis. Patient groups who benefit from perioperative therapy are not yet defined. The tumor microenvironment and circulating factors as possible predictors of response and prognosis gain interest. This study aimed to investigate cytokines in patients' serum and tumor tissue with regard to response and prognosis.
Median survival between SCC and AC was not different (published previously). Lower levels of CCL11 (Eotaxin-1) and CXCL10 (IP-10) in the tumor tissue were associated with a better prognosis (p = 0.022; p = 0.002). In the AC subgroup higher concentrations of TGF-β3 in serum and corresponding tumor tissue were associated with adverse prognosis (p = 0.035; p = 0.006). An association with histopathological response was found for IL-12(p70) and CXCL10 in patients' sera (p = 0.041; p = 0.032). The tissue levels of TGF-β1 and TGF-β2 were significantly lower in histopathological responders than in nonresponders (p = 0.033; p = 0.007). A similar trend was seen for TGF-β3, without statistical significance (p = 0.097).
Preoperative serum samples and corresponding tumor tissue (n = 54), only serum (n = 20) or only tissue (n = 4) were collected from patients undergoing surgery for cT3/4 esophageal squamous cell cancer (SCC) (n = 34) and adenocarcinoma (AC) (n = 44). All samples were taken after neoadjuvant treatment. All patients received perioperative chemo(radio)therapy. Cytokine levels of 17 different cytokines were measured by multiplex immunoassay and correlated with clinicopathological factors.
Two chemokines (CCL11 and CXCL10) in posttherapeutic tumor tissue were associated with prognosis in patients with esophageal cancer, lower levels indicating a better prognosis. Lower levels of TGF-β were associated with better response and prognosis in patients with AC.
食管癌通常以肿瘤生长侵袭性强和预后差为特征。从围手术期治疗中获益的患者群体尚未明确。肿瘤微环境和循环因子作为反应和预后的可能预测指标受到关注。本研究旨在调查患者血清和肿瘤组织中的细胞因子与反应和预后的关系。
鳞状细胞癌（SCC）和腺癌（AC）之间的中位生存期无差异（先前已发表）。肿瘤组织中较低水平的CCL11（嗜酸性粒细胞趋化因子-1）和CXCL10（IP-10）与较好的预后相关（p = 0.022；p = 0.002）。在AC亚组中，血清和相应肿瘤组织中较高浓度的TGF-β3与不良预后相关（p = 0.035；p = 0.006）。在患者血清中发现IL-12(p70)和CXCL10与组织病理学反应相关（p = 0.041；p = 0.032）。组织病理学反应者的TGF-β1和TGF-β2组织水平显著低于无反应者（p = 0.033；p = 0.007）。TGF-β3也有类似趋势，但无统计学意义（p = 0.097）。
从接受cT3/4食管鳞状细胞癌（SCC）（n = 34）和腺癌（AC）（n = 44）手术的患者中收集术前血清样本和相应肿瘤组织（n = 54）、仅血清（n = 20）或仅组织（n = 4）。所有样本均在新辅助治疗后采集。所有患者均接受围手术期化疗（放疗）。通过多重免疫测定法测量17种不同细胞因子的水平，并与临床病理因素相关联。
治疗后肿瘤组织中的两种趋化因子（CCL11和CXCL10）与食管癌患者的预后相关，水平较低表明预后较好。AC患者中较低水平的TGF-β与较好的反应和预后相关。
