Department of Medicine III, Charité-CBF, Hindenburgdamm 30, 12200, Berlin, Germany.
Cancer Immunol Immunother. 2013 Jul;62(7):1223-33. doi: 10.1007/s00262-013-1428-4. Epub 2013 Apr 27.
We analysed mRNA levels of interferon response genes (ISG15, STAT1, CXCL10) of inhibitors of the JAK/STAT pathway (STAT3, SOCS1, SOCS3) and of cytokines (TNFα, IL10, TGFß1) in peripheral blood of 91 stage III melanoma patients enrolled in EORTC 18991 trial to find biomarkers indicative for disease stage and predictive for efficacy of pegylated interferon alpha-2b (PEG-IFNα-2b) therapy. mRNA levels were analysed at baseline and after 6 months. Univariate and multivariate analyses were performed to estimate the prognostic and predictive role of mRNA levels for distant metastasis-free survival (DMFS) and relapse-free survival (RFS). Compared to healthy controls, melanoma patients showed significantly higher TGFβ1 mRNA levels. In a multivariate model, increasing SOCS1 and SOCS3 mRNA levels were associated with worse RFS (P = 0.02 and P = 0.04, respectively) and DMFS (P = 0.05 and P = 0.05, respectively) due to negative correlation between, respectively, SOCS1/SOCS3 mRNA levels and ulceration or Breslow thickness. No impact of PEG-IFNα-2b on mRNA levels was observed except for ISG15 mRNA levels, which decreased in the treatment arm (P = 0.001). It seems that patients with a decrease >60 % of ISG15 mRNA levels during 6 months PEG-IFNα-2b had inferior outcome.
我们分析了 EORTC 18991 试验中 91 例 III 期黑色素瘤患者外周血中 JAK/STAT 通路抑制剂（STAT3、SOCS1、SOCS3）和细胞因子（TNFα、IL10、TGFβ1）的干扰素反应基因（ISG15、STAT1、CXCL10）的 mRNA 水平，以寻找指示疾病分期的生物标志物，并预测聚乙二醇干扰素α-2b（PEG-IFNα-2b）治疗的疗效。在基线和 6 个月时分析了 mRNA 水平。进行了单变量和多变量分析，以估计 mRNA 水平对远处无转移生存率（DMFS）和无复发生存率（RFS）的预后和预测作用。与健康对照相比，黑色素瘤患者的 TGFβ1 mRNA 水平显著升高。在多变量模型中，SOCS1 和 SOCS3 mRNA 水平的增加与 RFS（P = 0.02 和 P = 0.04）和 DMFS（P = 0.05 和 P = 0.05）较差相关，原因分别是 SOCS1/SOCS3 mRNA 水平与溃疡或 Breslow 厚度之间存在负相关。除 ISG15 mRNA 水平外，PEG-IFNα-2b 对 mRNA 水平没有影响，ISG15 mRNA 水平在治疗组中降低（P = 0.001）。似乎在 6 个月 PEG-IFNα-2b 期间 ISG15 mRNA 水平降低>60%的患者结局较差。
