GDF 15 as an anti-apoptotic, diagnostic and prognostic marker in oral squamous cell carcinoma

Abstract

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.