Department of Thoracic Surgery, University Medical Center Freiburg, Freiburg, Germany.
PLoS One. 2012;7(7):e41746. doi: 10.1371/journal.pone.0041746. Epub 2012 Jul 25.
CC-chemokine ligand 18 (CCL18) is mainly expressed by alternatively activated macrophages and DCs and plays an important role in lung fibrosis, arthritis and other diseases. Here CCL18 was measured in sera of 31 healthy volunteers and 170 patients with lung cancer and correlated these data with histology, tumor stage and clinical parameters. Mean CCL18 serum level of the patients with non-small-cell lung cancer was 150(857) ng/ml vs. 32(61) ng/ml in the healthy control group. Patient groups differ significantly according their histology (adenocarcinoma 143(528) ng/ml vs squamous cell carcinoma 187(857) ng/ml, p<0.02). In addition, we found a significant difference between patients with lower versus higher T-stage (p<0.003). Receiver operating characteristic (ROC) analyses revealed a cutoff point of 83 ng/ml (area under the curve (AUC): 0.968; p<0.0001) to discriminate between healthy controls and non-small-cell lung cancer patients. ROC analyses to discriminate between patients, who died because of cancer related death and those who died for other reasons did not lead to a valid AUC. To stratify the tumor patients, a criterion value plot was performed leading to a point of equal sensitivity and specificity (54%) of 162 ng/ml. Patients with a CCL18 serum level higher than 160 ng/ml had a mean survival time of 623 days. In contrast, those in patients with a baseline level between 83 ng/ml and 160 ng/ml the mean survival time was 984 days (p<0.005). Survival-analysis revealed in adenocarcinoma a mean survival of 1152 days in the group below 83 ng/ml. In the median group the mean survival time was 788 days and in the group with the highest levels the mean survival time was 388 days (p<0.001). In contrast, we found no correlation between the FEV1 and the CCL18 baseline level. In conclusion, in patients suffering from adenocarcinoma increased serum CCL18 levels predict a diminished survival time.
CC-趋化因子配体 18（CCL18）主要由选择性激活的巨噬细胞和 DC 表达，在肺纤维化、关节炎等疾病中发挥重要作用。本研究检测了 31 名健康志愿者和 170 名肺癌患者的血清 CCL18 水平，并将这些数据与组织学、肿瘤分期和临床参数相关联。非小细胞肺癌患者的 CCL18 血清平均水平为 150（857）ng/ml，而健康对照组为 32（61）ng/ml。根据组织学，患者组之间存在显著差异（腺癌 143（528）ng/ml 与鳞状细胞癌 187（857）ng/ml，p<0.02）。此外，我们还发现 T 分期较低的患者与 T 分期较高的患者之间存在显著差异（p<0.003）。受试者工作特征（ROC）分析显示，83ng/ml 为区分健康对照组和非小细胞肺癌患者的最佳截断值（曲线下面积（AUC）：0.968；p<0.0001）。为了区分因癌症相关死亡和其他原因死亡的患者，ROC 分析未得出有效 AUC。为了对肿瘤患者进行分层，进行了标准值绘图，得出了一个敏感性和特异性均为 54%（162ng/ml）的平衡点。血清 CCL18 水平高于 160ng/ml 的患者的平均生存时间为 623 天。相比之下，血清 CCL18 基线水平在 83ng/ml 和 160ng/ml 之间的患者的平均生存时间为 984 天（p<0.005）。生存分析显示，在 CCL18 水平低于 83ng/ml 的腺癌组中，患者的平均生存时间为 1152 天。在中位数组中，平均生存时间为 788 天，在 CCL18 水平最高的组中，平均生存时间为 388 天（p<0.001）。相比之下，我们没有发现 FEV1 和 CCL18 基线水平之间存在相关性。综上所述，在患有腺癌的患者中，血清 CCL18 水平升高预示着生存时间缩短。
