Prognostic significance of serum hepatocyte growth factor in clear cell renal cell carcinoma: comparison with serum vascular endothelial growth factor

Abstract

: No adequate serum predictive biomarker currently exists, which can identify the activity of renal cell carcinoma (RCC). We investigate the association of serum hepatocyte growth factor (HGF) and serum vascular endothelial growth factor (VEGF) levels with clinicopathologic parameters in untreated clear cell RCC patients. We measured serum levels of HGF and VEGF in 45 patients with untreated clear cell RCC and 45 healthy controls using an enzyme-linked immunosorbent assay (ELISA). Patients with clear cell RCC had significantly higher serum HGF and VEGF concentrations than healthy subjects : median, 1070.7 versus 728.3 pg/ml (p 0.0001) for HGF ; and median, 397.5 versus 245.6 pg/ml (p=0.0003) for VEGF. We found a significant correlation between serum level of HGF and clinical stage and tumor grade. Survival of patients with high serum HGF ( 1150 pg/ml) was significantly reduced compared to patients with low serum HGF concentrations (p=0.0044). In patients with nuclear grade 2 or high stage RCC, the higher serum HGF group exhibited significantly lower cause-specific survival (p= 0.0087 and p 0.05, respectively). No significant difference was observed between serum VEGF levels and cause-specific survival rate. Serum HGF might be a diagnostic and prognostic indicator in clear cell RCC, especially for patients with grade 2 or high stage RCC.

MET and MST1R as prognostic factors for classical Hodgkin's lymphoma

“…In striking contrast to our results, expression of MET/HGF in solid malignancies has been associated with unfavorable clinical outcomes, 16,17,19,20,22,25 although a few studies identified a favorable prognostic impact of MET. 36,37 Expression of MST1R is also associated with unfavorable clinical outcomes [38][39][40] or not associated with prognosis.…”

“…ovary, 19 kidney, 20 lung, 21 and thyroid carcinomas. 22 Downregulation of MET expression by an antagonistic anti-MET antibody or small interfering RNA inhibits cellular proliferation and motility in lung cancer 23 and medullary thyroid cancer.…”

“…24 Previous studies also report that MET/HGF has prognostic significance in many malignant tumors. 19,20,25 MST1R (RON), an RTK with homology to MET, is involved in tumor progression and metastasis. 26,27 MST1R is overexpressed in human epithelial malignancies.…”

Exploitation of Aberrant Signalling Pathways as Useful Targets for Renal Clear Cell Carcinoma Therapy

“…Moreover, VHL-negative RCC cells exhibit cell invasion and branching morphogenesis in response to HGF (Koochekpour et al, 1999). c-MET has also been shown to be constitutively phosphorylated in RCC and high levels of serum HGF/SF in RCC patients are associated with reduced survival (Tanimoto et al, 2008). Presently, MET is being targeted in clinical trials for the treatment of RCC (Giubellino et al, 2009).…”

The prognostic value of vascular endothelial growth factor in patients with renal cell carcinoma: a systematic review of the literature and meta-analysis

“…Recent study has shown that a high serum VEGF level is associated with an increased risk of recurrence and cancer-specific death in patients with RCC [11]. On the other hand, earlier studies did not find an association with VEGF level and RCC prognosis [12,13]. There have also been some inconsistencies with respect to the prognostic value of VEGF tumor expression in RCC [14].…”