Upregulation of nucleus HDGF predicts poor prognostic outcome in patients with penile squamous cell carcinoma bypass VEGF-A and Ki-67

Abstract

Hepatoma-derived growth factor (HDGF) has been verified to serve as a credible prognostic marker for several types of cancers, but its role in urologic carcinomas remains undetermined. In this study, we analyzed the significance of HDGF, as well as its relative factors such as vascular endothelial growth factor-A (VEGF-A) and Ki-67, in penile squamous cell carcinoma (PSCC). Formalin-fixed paraffin-embedded PSCC samples from 54 patients receiving surgery at Qilu Hospital of Shandong University were included in the retrospective study. The expressions of HDGF, VEGF-A, and Ki-67 were detected by immunohistochemistry of a non-biotin polymerized horseradish peroxidase method. The relationships between the expressions of HDGF and VEGF-A, Ki-67 were assessed. Moreover, their correlations with clinical pathologic characteristics and disease prognosis were, respectively, evaluated. HDGF, VEGF-A, and Ki-67 were positively expressed in 28 (51.9%), 29 (53.7%), and 26 (48.1%) patients, respectively. The expressions of VEGF-A and Ki-67 were closely correlated with PSCC type (P < 0.05). A statistically significant relationship between the expressions of HDGF and VEGF-A in PSCC was observed (P = 0.03). Patients with symptom interval of more than 6 months had a significantly poorer survival rate than those with symptom interval less than 6 months (43.3 vs. 70.8%, P = 0.043). Patients with positive HDGF expression also showed a significantly poorer survival rate than those with negative HDGF expression (39.3 vs. 73.1%, P = 0.013). Logistic regression demonstrated that the expression level of HDGF was an independent predictor for the prognosis of postoperative patients. The expression of HDGF significantly correlated with VEGF-A, but not Ki-67 expression. Overexpression of HDGF, rather than VEGF-A or Ki-67, was confirmed to be an independent prognosticator of poor outcome for PSCC patients.