Clinical significance of platelet derived growth factor-C and -D in gastric cancer.

ABSTRACT

Platelet-derived growth factor (PDGF)-C and PDGF-D are frequently upregulated in human cancers and play important roles in tumor progression, angiogenesis and metastasis. However, the distribution, frequency and prognostic value of PDGF-C and PDGF-D expression in gastric cancer have not been clarified. The present study evaluated the association between expression of PDGF-C and PDGF-D, clinicopathological factors and outcomes, in patients with gastric cancer. Gastric adenocarcinoma tumor samples were obtained from 204 patients who underwent curative gastrectomy between 2003 and 2007. The expression of PDGF-C and PDGF-D was analyzed by immunohistochemical staining. High expression of PDGF-C and PDGF-D was detected in 114 (56%) and 151 (74%) tumors, respectively. PDGF-D expression was significantly associated with tumor depth (P=0.039), histopathology (P<0.01), tumor stage (P=0.01) and recurrence (P<0.01), whereas PDGF-C expression correlated only with histopathology (P=0.05). High PDGF-D expression was also associated with significantly shorter relapse-free survival (RFS) time (P<0.01), whilst high PDGF-C expression was associated with marginally, but not significantly, shorter RFS (P=0.10). On multivariate analysis, high PDGF-D expression was determined to be an independent prognostic factor (hazard ratio, 3.3; 95% confidence interval, 1.20-9.4; P=0.02). These findings indicate that high PDGF-D expression is strongly associated with tumor progression, recurrence, distant metastasis and poor outcomes in patients with gastric cancer. PDGF-D may therefore be an independent prognostic factor and a novel therapeutic target.