MET is a predictive factor for late recurrence but not for overall survival of early stage hepatocellular carcinoma

Abstract

The MET and RON receptors are tyrosine kinases that form a non-covalent complex on the cell surface that functions in several steps of tumor progression. The purpose of this study was to determine the clinical significance of MET and RON expression on long-term survival and recurrence after curative resection in a large cohort of hepatocellular carcinoma (HCC) patients. We performed immunohistochemical analyses on microarrays of the tumors using antibodies against MET and RON. We evaluated the prognostic value of biomarker expression using Cox regression and the Kaplan-Meier method in 490 HCC patients. MET-positive patients had higher overall recurrence rates than MET-negative patients (P = 0.041); however, MET positivity was not associated with overall survival (OS) (P = .249). RON was not associated with overall recurrence rates and OS. MET was independently associated with late but not early phase recurrence. Particularly, the prognostic significance of MET is limited in early stage disease. MET+/RON+ patients had higher overall recurrence rates than those with the other expression patterns (P = 0.071), although the result did not reach statistical significance. Immunohistological activation of MET expression has no prognostic significance for OS in patients with HCC. However, MET positivity was correlated with late recurrence after HCC resection in early stage disease.

Prognostic value of c-Met overexpression in hepatocellular carcinoma: a meta-analysis and review

“…Of the remaining 9 potentially eligible studies, 4 were further excluded by the inclusion criteria: one was conducted in advanced HCC [ 20 ] and three had no data from which the required hazard ratio (HR) with 95% confidence interval (CI) stratified by the c-Met status (low or high) could be extracted [ 21 – 23 ]. Finally, 5 studies were included in the meta-analysis [ 24 – 28 ].…”

“…The criteria are briefly summarized in the Table 1 . The rate of high c-Met expression ranged from 25.4% [ 27 ] to 61.2% [ 28 ].…”

“…From three studies [ 24 – 28 ], 1,356 patients were included in the meta-analysis of HRs for relapse-free survival (RFS). Compared with HCC patients with low c-Met expression, patients with c-Met-high HCC showed significantly worse RFS (HR = 1.26 [95% CI, 1.02–1.56], P = 0.03) (Figure 2A ).…”

“…The overexpression of c-Met has also been observed in HCC [ 20 – 28 ]. However, its prognostic impact has not been consistent among studies.…”

Platelet-derived growth factor receptor α in hepatocellular carcinoma is a prognostic marker independent of underlying liver cirrhosis

“…Very low proportion of PDGFRα strong positive patients would hinder the usefulness of PDGFRα as HCC target. On the other hands, it has been investigated that overexpression of vascular endothelial growth factor (VEGF) which was shown in about 20% of HCC patients tended to result in shortened overall survival [17], and inhibition and MET in MET-positive HCC which consist about 30-40% of HCC patients resulted in decreased tumor burden [28, 29]. Further studies that provide more consistent information on the proportion of PDGFRα positive HCC would put PDGFRα as a target for HCC treatment in the future.…”