Department of Oral and Maxillofacial Surgery, Plastic Surgery, University Medical Center of the Johannes Gutenberg-University, Augustusplatz 2, Mainz, Germany.
Oral Oncol. 2012 Jul;48(7):608-14. doi: 10.1016/j.oraloncology.2012.01.020. Epub 2012 Feb 16.
Growth-differentiation factor 15 (GDF 15) is involved in tumor pathogenesis and its expression is increased in many types of cancers. Functional effects of GDF 15 on oncogenesis of oral squamous cell carcinoma (OSCC) remain unclear. Therefore, the aim of this study was to examine the apoptotic characteristics of GDF 15 in OSCC cell lines in vitro and to analyze serum GDF 15 concentrations as a diagnostic and prognostic tumor marker for OSCC in vivo. Caspase activity was assessed in OSCC cell lines with the Caspase-Glo 3/7 system. Serum GDF 15 concentrations from 64 patients with histopathological proven OSCC and from 30 healthy volunteers were measured using an enzyme-linked immunosorbent assay. In 21 patients, serum GDF 15 was also analyzed postoperatively. In vitro, treatment of OSCC cell lines with GDF 15 reduced Caspase 3/7 activity significantly (p<0.05). In vivo, serum GDF 15 concentrations of the OSCC patients in all stages of OSCC were significantly higher than those of the healthy subjects (p<0.0001). After surgery, GDF 15 concentrations declined significantly from 1545±774pg/ml preoperative to 953±438pg/ml postoperative (p=0.003). The median survival time of OSCC patients with GDF 15 levels below 875pg/ml was significantly higher than of OSCC patients with GDF 15 levels above or equal 875pg/ml (p=0.031). Determination of receiver operating characteristic curves (ROC) showed a respective area under the ROC curve (AUC) of 0.943. The anti-apoptotic effect of GDF 15 in OSCC cell lines was shown in vitro. In vivo, significant elevated serum GDF 15 levels with prognostic value in OSCC-patients were seen for the first time. The results indicate that GDF15 may be used as a potential marker for diagnosis and prognosis of this entity.
生长分化因子 15（GDF15）参与肿瘤发病机制，其表达在许多类型的癌症中增加。GDF15 对口腔鳞状细胞癌（OSCC）发生的功能影响尚不清楚。因此，本研究旨在研究 GDF15 在体外 OSCC 细胞系中的凋亡特征，并分析血清 GDF15 浓度作为体内 OSCC 的诊断和预后肿瘤标志物。使用 Caspase-Glo 3/7 系统评估 OSCC 细胞系中的半胱天冬酶活性。使用酶联免疫吸附试验测量 64 例经组织病理学证实的 OSCC 患者和 30 名健康志愿者的血清 GDF15 浓度。在 21 名患者中，还分析了术后血清 GDF15。在体外，用 GDF15 处理 OSCC 细胞系可显著降低 Caspase 3/7 活性（p<0.05）。在体内，所有阶段的 OSCC 患者的血清 GDF15 浓度均明显高于健康受试者（p<0.0001）。手术后，GDF15 浓度从术前的 1545±774pg/ml 显著下降至术后的 953±438pg/ml（p=0.003）。GDF15 水平低于 875pg/ml 的 OSCC 患者的中位生存时间明显长于 GDF15 水平高于或等于 875pg/ml 的 OSCC 患者（p=0.031）。确定接收者操作特征曲线（ROC）的曲线下面积（AUC）分别为 0.943。在体外显示了 GDF15 在 OSCC 细胞系中的抗凋亡作用。在体内，首次发现 GDF15 水平升高与 OSCC 患者的预后相关。结果表明，GDF15 可用作该实体的潜在诊断和预后标志物。
