Vihinen Pia, Kallioinen Minna, Vuoristo Meri-Sisko, Ivaska Johanna, Syrjänen Kari J, Hahka-Kemppinen Marjo, Kellokumpu-Lehtinen Pirkko-Liisa, Pyrhönen Seppo O
Department of Oncology and Radiotherapy, Turku University Hospital, POB 52, Turku 20521, Finland.
Clin Exp Metastasis. 2007;24(7):567-74. doi: 10.1007/s10585-007-9093-7. Epub 2007 Aug 29.
This work was conducted to find out new potential serum markers and study their role as predictive factors in patients with metastatic melanoma. Serum samples from 68 patients with stage IV malignant melanoma were collected just before current treatment and screened for 79 different cytokines by using a multi-cytokine array. Angiogenin, which is a protein capable of promoting angiogenesis, was found to be markedly elevated among a sub-group of patients with progressive disease (PD) and thus was subjected to further analysis. The mean serum angiogenin level was 270 ng/ml and the median 236 ng/ml (STD 163 ng/ml). Concentrations were significantly higher among men than in women (P = 0.031), whereas patient's age, site of the primary tumour, Clark's or Breslow's classifications were not associated with angiogenin levels. Patients with only lymph node metastases had markedly lower angiogenin levels than those with metastases at other sites (P = 0.05). High angiogenin levels were significantly (P = 0.015; Kruskal-Wallis) associated with poor treatment response with chemoimmunotherapy. Treatment-related survival (TRS) was shorter (10 months) in patients with above-median values than in those with below-median levels (19 months, P = NS). Cox multivariate regression model was used to control for the confounding by the classical prognostic factors of melanoma (age, sex, disease burden, performance score, site of metastases). Disease burden was the only variable that remained in the model as a significant independent predictor of TRS (P = 0.044). These data suggest that serum angiogenin levels might be of predictive value in the evaluation of treatment response for patients with stage IV melanoma.
开展这项研究是为了找出新的潜在血清标志物，并研究它们在转移性黑色素瘤患者中作为预测因素的作用。在当前治疗前收集了68例IV期恶性黑色素瘤患者的血清样本，并使用多细胞因子阵列对79种不同的细胞因子进行筛查。血管生成素是一种能够促进血管生成的蛋白质，发现在疾病进展（PD）亚组患者中显著升高，因此对其进行了进一步分析。血清血管生成素平均水平为270 ng/ml，中位数为236 ng/ml（标准差163 ng/ml）。男性的浓度显著高于女性（P = 0.031），而患者的年龄、原发肿瘤部位、克拉克或布雷斯洛分类与血管生成素水平无关。仅发生淋巴结转移的患者血管生成素水平明显低于其他部位转移的患者（P = 0.05）。血管生成素水平高与化疗免疫治疗的治疗反应差显著相关（P = 0.015；Kruskal-Wallis检验）。血管生成素水平高于中位数的患者的治疗相关生存期（TRS）较短（10个月），低于中位数水平的患者为19个月（P = 无显著性差异）。使用Cox多变量回归模型来控制黑色素瘤经典预后因素（年龄、性别、疾病负担、体能状态评分、转移部位）的混杂影响。疾病负担是模型中唯一作为TRS显著独立预测因子保留的变量（P = 0.044）。这些数据表明，血清血管生成素水平在评估IV期黑色素瘤患者的治疗反应中可能具有预测价值。
