Identification of Pancreatic Cancer in Biliary Obstruction Patients by FRY Site-specific Methylation

Background: Methylation at cg 16941656 of FRY is exclusively found in normal pancreatic tissue and has been proven to be specific for pancreatic-in-origin among several adenocarcinomas. Here, we investigated methylated DNA in the bile as a biomarker to differentiate the cause of obstruction between pancreatic cancer and benign causes. Materials and Methods: Bile samples of 45 patients with obstructive jaundice who underwent ERCP were collected and classified into pancreatic cancer (group 1) and benign causes (group 2) in 24 and 21 patients, respectively. DNA was extracted from bile and bisulfite modification was performed. After, methylation in cg 16941656 of FRY was identified by real-time PCR, with beta-actin used as a positive control. Results: Methylated DNA was identified in 10/24 (41.67%) and 1/21 (4.8%) of cases in groups 1 and 2, respectively (P= 0.012). The sensitivity, specificity, positive predictive value and negative predictive value to differentiate pancreatic cancer from benign causes were 42%, 95%, 91%, and 59%, respectively. Conclusions: Detecting a methylation at cg 16941656 of FRY in bile has high specificity, with an acceptable positive likelihood rate, and may therefore be helpful in distinguish pancreatic cancer from benign strictures.