Prognostic significance of c-Met, β-catenin and FAK in patients with hepatocellular carcinoma following surgery

Abstract

Abstract. The present study aimed to investigate the prognostic value of specific molecular markers in patients with hepatocellular carcinoma (HCC) who had received surgery. Immunohistochemical analysis was used to measure the expression of hepatocyte growth factor receptor (c-Met), β-catenin and focal adhesion kinase (FAK) in patients with HCC. c-Met expression was identified to be high in patients with larger tumors, higher α-fetoprotein (AFP) levels, higher Edmondson grades, portal vein invasion and higher tumor-node-metastasis (TNM) stages. FAK expression was high in patients with portal vein invasion, higher Edmondson grades and higher TNM stages. β-catenin expression was high in patients with larger tumors, hepatitis B virus (HBV) infection, portal vein invasion, higher Edmondson grades and higher TNM stages. Following multivariate analysis, FAK (P= 0.002) and β-catenin (P= 0.006) expression levels were demonstrated to be significantly associated with Edmondson grade. Additionally, the tumor size (P= 0.009) and HBV infection status (P= 0.002) were revealed to be associated with β-catenin expression. Kaplan-Meier survival curve analysis demonstrated that patients with HCC with higher FAK expression, higher β-catenin expression, portal vein invasion, higher Edmondson grades, higher TNM stages, younger ages and higher AFP levels had significantly poorer prognoses. Cox's regression analysis revealed that the survival period was correlated with the Edmondson grade, age, AFP level, and FAK and β-catenin expression. Univariate analysis of c-Met, β-catenin and FAK identified a significant correlation between FAK and β-catenin (P= 0.015). Correlation analysis revealed no significant correlation between the three molecular markers, but β-catenin and c-Met were markedly correlated (P=0.052). No significant correlation between FAK, c-Met or β-catenin expression was identified. FAK and β-catenin expression demonstrated a correlation with a range of clinicopathological factors, and high FAK and β-catenin expression levels were identified to be correlated with a poor survival rate of patients with HCC. Thus, patients with higher FAK and β-catenin expression may require more aggressive therapy. The results of the present study suggest that FAK and β-catenin expression possess more prognostic value than c-Met expression in patients with HCC.

The Function of the HGF/c-Met Axis in Hepatocellular Carcinoma

“…Nevertheless, another study (Ke et al, 2009) showed that c-Met was not an independent prognostic factor of HCC for OS and cumulative recurrence, but the combination of c-Met/CD151 was. Meanwhile, an other study (Gong et al, 2018) also suggested that the prognostic value of c-Met is contradictory. By univariate analysis, c-Met overexpression was significantly correlated with clinicopathological factors, but not with multivariate analysis.…”

CYP1A2 suppresses hepatocellular carcinoma through antagonizing HGF/MET signaling

“…Vascular invasion is a prognostic marker correlated with early HCC recurrence 48 . On the contrary, it has been reported that a high MET level was identified in HCC patients with higher AFP and more frequent portal vein invasion 49 .…”

Interferon-α Combined With Herbal Compound “Songyou Yin” Effectively Inhibits the Increased Invasiveness and Metastasis by Insufficient Radiofrequency Ablation of Hepatocellular Carcinoma in an Animal Model

“…As a key factor in the Wnt/β-catenin signal pathway, β-catenin plays an important role in HCC progression, phenotype changes, and metastasis. 34 - 36 Mutations involving the Wnt/β-catenin pathway appear to be one of the most frequent genetic events that contribute to liver carcinogenesis and progression. 36 Moreover, the correlation between β-catenin signaling and EMT has been examined in several research studies.…”