Hepatocyte growth factor, transforming growth factor α, and their receptors as combined markers of prognosis in hepatocellular carcinoma

Abstract

A change in the balance between proliferation and apoptosis in the course of hepatocellular carcinoma (HCC) development and progression has been suspected. We wanted to identify related genes whose mRNA levels could provide markers of severity and prognosis after resection. The extent of cell apoptosis, proliferation, and differentiation was measured with a terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate-biotin nick-end labeling assay, and the Ki-67 index was determined in paired tumor and cirrhotic tissue samples from patients who had undergone HCC resection after diagnosis of hepatitis C-related or alcoholism-related cirrhosis. These patients included two groups with highly versus poorly differentiated tumor cells, and the latter was split into two subgroups of those with versus without early recurrence. The mRNA levels for various apoptosis-related or proliferation-related genes and those for the growth factor/receptor systems were measured by quantitative reverse transcriptase-polymerase chain reaction in paired tumor and cirrhotic liver samples from every patient, and some of the corresponding proteins were detected by immunohistochemistry. In all instances, protein expression was highly heterogeneous within groups and similar between groups. In contrast, some differences in mRNA level between tumor and cirrhotic tissues were quite informative. Low levels of hepatocyte growth factor and transforming growth factor alpha mRNAs were found concomitantly in highly differentiated tumors, whereas overexpression of mRNAs for the cognate receptors c-met and epidermal growth factor receptor were found in poorly differentiated tumors and primarily in patients with early tumor recurrence. These results argue for growth factor-dependent HCC development and provide novel and combined prognosis markers after HCC surgery.

Dysregulation of growth factor signaling in human hepatocellular carcinoma

“…Additionally, overexpression of MET is detected predominantly in poorly differentiated HCCs (Daveau et al, 2003). Although one study does not demonstrate a correlation of HGF expression levels with patient survival or clinicopathological parameters (Ueki et al, 1997), recently published data show that higher HGF serum levels negatively correlate with patient survival time (Vejchapipat et al, 2004) and positively correlate with tumor size (Yamagamim et al, 2002).…”

Crosstalk between EGFR and p53 in Hepatocellular Carcinoma

“…In previous studies, overexpression of EGFR in HCC, varies from 3% to 85% (Nakopoulou et al, 1994;Yamaguchi et al, 1995;Altimari et al, 2003;Daveau et al, 2003;Hua et al, 2011). In addition, several studies found that overexpression of EGFR is correlated with early tumor recurrence and a poor prognostic in high grade HCCs (Yamaguchi et al, 1995;Daveau et al, 2003). In this study, we demonstrated that EGFR is overexpressed in 38% of HCCs, which is consistent with Bassullu N et al study (2012).…”

“…Overexpression of EGFR was found in several human cancers, including HCC (Fan et al 2014). In previous studies, overexpression of EGFR in HCC, varies from 3% to 85% (Nakopoulou et al, 1994;Yamaguchi et al, 1995;Altimari et al, 2003;Daveau et al, 2003;Hua et al, 2011). In addition, several studies found that overexpression of EGFR is correlated with early tumor recurrence and a poor prognostic in high grade HCCs (Yamaguchi et al, 1995;Daveau et al, 2003).…”

Real-time cellular and molecular dynamics of bi-metallic self-therapeutic nanoparticle in cancer cells

“…The possible mechanism for this can be explained as the overexpression of c-MET mRNA is a prominent event in liver cancer which is triggered by cytokines like IL-6, TNF-α and TGF-β (Granito et al 2015). In addition, the enhanced expression of c-MET allows increased binding of HGF proteins on it which stimulates several cancer pathways for enhanced cell growth, invasion and protection from apoptosis (Webb et al 1998;Daveau et al 2003;Sierra and Tsao 2011;Lee et al 2013). Thus downregulation of c-MET and hURP protein important for cancer cell progression after Gd-SPIO nanoparticles exposure provide evidence for anti-cancer effect of these nanoparticles.…”