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.

Prognostic Role of Hepatoma-derived Growth Factor in Solid Tumors of Eastern Asia: a Systematic Review and Meta-Analysis

“…The following articles were also excluded: three duplicated publications (Zhou et al, 2007b;Zhou et al, 2010a;Yang et al, 2014); three without data for HR and 95%CI calculations and adequate contact with the investigators could not be established (Natrajan et al, 2006;Mao et al, 2008;Hanada et al, 2013); two with a sample size<50 (Hsu et al, 2012;Tao et al, 2014); two in which HDGF expression was not detected by IHC methods (Savola et al, 2009;Zhang et al, 2010); three uncorrelated. Finally, 26 cohort studies were found eligible for the meta-analysis (Hu et al, 2003;Ren et al, 2004;Iwasaki et al, 2005;Uyama et al, 2006;Yamamoto et al, 2006;Yoshida et al, 2006;Chang et al, 2007;Yamamoto et al, 2007;Zhou et al, 2007a;Hu et al, 2009;Zhou et al, 2010b;Liu et al, 2011;Wang et al, 2011;Zhang et al, 2011;Chen et al, 2012a;Chen et al, 2012b;Lin et al, 2012;Han et al, 2013;Li et al, 2013a;Li et al, 2013b;Li et al, 2013c;Yang et al, 2013;Guo et al, 2014b;Song et al, 2014;Wang et al, 2014;Zhang et al, 2014), containing 32 datasets (29 datasets for OS; 17 datasets for DFS) were qualified to the standard of the meta-analysis. The main characteristics of the selected studies were summari...…”

“…In recent years, elevated levels of hepatoma-derived growth factor (HDGF) have been observed in a variety of malignancies and high levels of HDGF appears to be associated with increased malignancy across cancers, as witnessed by the correlation with adverse characteristics such as poor patient survival (Hu et al, 2003;Ren et al, 2004;Iwasaki et al, 2005;Uyama et al, 2006;Yamamoto et al, 2006;Yoshida et al, 2006;Chang et al, 2007;Yamamoto et al, 2007;Zhou et al, 2007a;Hu et al, 2009;Savola et al, 2009;Zhang et al, 2010;Zhou et al, 2010b;Liu et al, 2011;Wang et al, 2011;Ye et al, 2011;Zhang et al, 2011;Chen et al, 2012a;Chen et al, 2012b;Hsu et al, 2012;Lin et al, 2012;Han et al, 2013;Hanada et al, 2013;Li et al, 2013a;Li et al, 2013b;Li et al, 2013c;Yang et al, 2013;Guo et al, 2014b;Song et al, 2014;Wang et al, 2014;Yang et al, 2014;Zhang et al, 2014). As a multifunctional protein Bao et al, 2014) widely expressed by many types of human cells, HDGF is involved in the regulations of a myriad of cancer cell activities during cancer transformation (Yang et al, 2013), apoptosis , angiogenesis (Ren et al, 2009), and metastasis (Chen et al, 2012a).…”

Hepatoma-Derived Growth Factor Upregulation Is Correlated with Prognostic Factors of Early-Stage Cervical Adenocarcinoma

“…In the current study, we demonstrated that an increased HDGF expression was present in poorly differentiated Cx (Hela) cells and was associated with tumor progression [ 20 , 21 , 22 , 23 ]. Recently, inhibition of HDGF expression has been shown to repress the proliferation of hepatoma cells to varying degrees [ 12 ]. This is consistent with our findings of a differential HDGF expression in cervical adenocarcinoma tissues.…”

“…HDGF has a mitogenic function in various cells, such as human hepatocellular carcinoma cells, fibroblasts, endothelial cells, vascular smooth muscle cells and fetal hepatocytes [ 11 ]. Although the specific function of this protein is unknown, recent studies have suggested that HDGF plays a role in the regulation of cancer development [ 12 ]. Therefore, we hypothesized that the HDGF expression in human malignant tumors may also have an important functional role in metastasis and may consequently influence the prognosis of patients.…”

The Evolving Landscape in Advanced Penile Cancer

“…Paclitaxel is active in penile cancer [7], while pazopanib inhibits a number of tyrosine kinases, including the VEGF receptor. The VEGF receptor is activated by the VEGF–A ligand which has been found to be overexpressed in approximately 50% of penile cancer cases [12]. Another chemotherapy agent with antiangiogeneic properties, vinflunin, is being investigated in small ongoing trial.…”