DOI: 10.1097/mpa.0000000000002692 ISSN: 1536-4828

Exploring the Role of MET Gene as a Potential Biomarker and Therapeutic Target in Ampullary Cancer

Apurva, Arun Kumar, Abhay Kumar Sharma, Nimisha, Ejaj Ahmad, Vineeta Vijay Batra, Seneha Santoshi, Sundeep Singh Saluja
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Background:

The incidence of Ampullary carcinoma (AC) has dramatically increased. Nearly 50% of patients develop recurrence indicating need for additional prognostic markers and treatment options. Emerging evidence suggests that Mesenchymal Epithelial Transition (MET) genes play a role in tumorigenesis and can be a useful therapeutic target, however, its role in AC remains unexplored.

Methods:

This study investigated the methylation status using methylation specific PCR, mRNA expression using quantitative PCR and protein expression using Immunohistochemistry of the MET proto-oncogene in 61 surgically resected AC specimens and further examined its co-expression with HER2.

Results:

Our findings revealed MET promoter hypomethylation (68.85%), increased expression of MET at mRNA (67.21%) and protein level (54%) in ACs patients. Significant correlation was observed between both hypomethylation and increased mRNA expression ( P =0.026; P <0.000), and MET mRNA and protein expression ( P =0.037). Further, MET expression was notably higher in early stage ( P =0.003) and Intestinal-type (84.21%) than Pancreatobiliary type (PB-type) (61.76%) ( P =0.199). Additionally, co-expression of MET and HER2 receptors occurred in a significant subset of cases in AC suggesting receptor tyrosine kinase convergence ( P =0.014). In silico analysis of the GSE60979, dataset corroborated these findings, showing increased MET and ERBB2 (HER2) expression in tumor samples compared to normal tissues. At a median follow-up of 34 months the mean survival of AC patient was 37.3±2.5 months.

Conclusions:

These findings demonstrate that MET dysregulation is a recurrent molecular event in ampullary carcinoma and support further investigation of MET and HER2 co-expression as a basis for future mechanistic and therapeutic studies.

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