可溶性 Fas 配体作为分化型甲状腺癌疾病复发的生物标志物。
Soluble FAS ligand as a biomarker of disease recurrence in differentiated thyroid cancer.
机构信息
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia, USA.
出版信息
Cancer. 2013 Apr 15;119(8):1503-11. doi: 10.1002/cncr.27937. Epub 2013 Jan 22.
BACKGROUND
Reliable predictive biomarkers are required to address the challenge of disease recurrence after thyroid cancer surgery. For this study, the authors assessed the association of cellular-based and serum-based immunologic mediators with thyroid cancer recurrence.
METHODS
Leukocyte subset counts and immune regulatory cytokine levels were determined in peripheral blood samples using multiparameter flow cytometry and 51-panel, multiplex enzyme-linked immunosorbent assays, respectively. The functional activity of circulating B-lymphocytes, T-lymphocytes, and natural killer lymphocytes was assessed ex vivo. Differences in mean biomarker levels between defined patient groups and correlations between biomarkers and cancer recurrence were assessed using t tests or Wilcoxon tests and by univariate and multivariate analyses with Cox models. Optimal cutoff values of significantly correlated biomarkers that best predicted disease recurrence after surgery were established by receiver operating characteristics and were validated by using an optimal cutpoint determination algorithm.
RESULTS
In total, 35 patients were enrolled (median age, 49.4 year), including 24 women and 15 patients with recurrent disease; and there were 21 individuals in the control group. Patients without recurrence had higher levels of soluble FAS (tumor necrosis receptor superfamily, member 6) ligand (sFASL), transforming growth factor-β, regulatory T cells, and programmed death 1/ programmed death ligand 1-expressing leukocytes. sFASL (hazard ratio, 0.60; 95% confidence interval, 0.38-0.95; P = .031) and interferon-α (hazard ratio, 1.55; 95% confidence interval, 1.03-2.34; P = .038) were associated significantly with disease recurrence. There was a significant difference in progression-free survival between patient groups stratified by an sFASL optimal cutpoint of 15 pg/mL (log-rank P = .0009).
CONCLUSIONS
sFASL and IFN-α levels were correlated significantly with thyroid cancer recurrence and may be useful for risk-adapted surveillance strategies in patients with thyroid cancer.
背景
需要可靠的预测生物标志物来应对甲状腺癌手术后疾病复发的挑战。为此，作者评估了细胞和血清免疫介质与甲状腺癌复发的关系。
方法
使用多参数流式细胞术和 51 个面板、多重酶联免疫吸附试验分别测定外周血样本中的白细胞亚群计数和免疫调节细胞因子水平。评估循环 B 淋巴细胞、T 淋巴细胞和自然杀伤淋巴细胞的体外功能活性。使用 t 检验或 Wilcoxon 检验评估不同定义的患者组之间平均生物标志物水平的差异，并通过单变量和多变量分析与 Cox 模型评估生物标志物与癌症复发的相关性。通过接收者操作特征建立最佳截断值来确定具有显著相关性的生物标志物，以最佳预测手术后疾病复发，并使用最佳截断点确定算法进行验证。
结果
共纳入 35 例患者（中位年龄 49.4 岁），包括 24 例女性和 15 例复发患者，对照组 21 例。无复发患者可溶性 FAS（肿瘤坏死受体超家族成员 6）配体（sFASL）、转化生长因子-β、调节性 T 细胞和程序性死亡 1/程序性死亡配体 1 表达白细胞水平较高。sFASL（危险比，0.60；95%置信区间，0.38-0.95；P =.031）和干扰素-α（危险比，1.55；95%置信区间，1.03-2.34；P =.038）与疾病复发显著相关。根据 sFASL 最佳截断值 15 pg/mL 分层的患者组之间无进展生存率有显著差异（对数秩检验 P =.0009）。
结论
sFASL 和 IFN-α 水平与甲状腺癌复发显著相关，可能对甲状腺癌患者的风险适应监测策略有用。
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