MET gene as biomarker and potential therapeutic target in Ampullary cancer

The incidence of Ampullary carcinoma (AC) has dramatically increased. Nearly 50% of patients develop recurrence indicating need for additional prognostic marker and treatment options. Emerging evidence suggests that MET genes play a role in tumorigenesis and can be a useful therapeutic target, however, its role in AC remains unexplored. In the current study we investigated methylation, mRNA and protein expression of MET in 61 AC cases and assessed its effect on survival outcomes. We also cross-examined HER2 expression from our previous study in relation to MET expression in AC. Our findings revealed unmethylation (72.13%), increased expression of MET at mRNA (67.21%) and protein (54%) level in ACs patients. Significant correlation was observed between both unmethylation and increased mRNA expression (p-0.026; p-0.000), MET mRNA and protein expression (p-0.037). Further, MET expression was higher in early stage (p-0.003) and I-type (84.21%) than PB-type Acs (61.76%) (p=0.199). Our findings also revealed a co-expression of MET and HER2 receptors in AC. (p=0.014). At a median follow-up of 34 months the mean survival was 37.3 ± 2.5 months. Molecular parameters did not influence the survival outcome. These findings underscore the importance of MET gene in onset of Ampullary cancer. It can act as a diagnostic biomarker and therapeutic target warranting further investigation into its role in disease progression and RTK inhibitor targeted therapy.