title: SERPINB5 Promoter Hypomethylation Differentiates Pancreatic Ductal Adenocarcinoma From Pancreatitis.
abstract: OBJECTIVE
  The diagnosis of pancreatic ductal adenocarcinoma (PDAC) is challenging in the setting of pancreatitis. We investigated SERPINB5 for its impact on PDAC tumor biology and its use as a diagnostic marker for PDAC in the setting of pancreatitis.
  
  
  METHODS
  Patient samples from PDAC primary tumors, PDAC lymph node metastases, and pancreatitis were investigated for SERPINB5 promoter methylation by methylation-specific polymerase chain reaction (PCR). Six PDAC cell lines were investigated in vitro and in vivo using an orthotopic mouse model to generate primary tumors and metastases. SERPINB5 mRNA expression, protein expression, and promoter methylation were determined by quantitative reverse transcriptase-PCR, methylation-specific PCR, and Western Blot.
  
  
  RESULTS
  In patient samples, detection of an unmethylated SERPINB5 promoter differentiated pancreatitis from PDAC with a sensitivity of 57% and a specificity of 95% (P < 0.001). SERPINB5 was not deregulated in primary tumors versus metastases, but primary tumors without SERPINB5 protein expression had significantly reduced viability (P = 0.02).
  
  
  CONCLUSIONS
  SERPINB5 seems to assume an oncogenic role in PDAC. In clinical samples, detection of unmethylated SERPINB5 was a specific marker for PDAC even in the context of pancreatitis and may provide the basis for a liquid biopsy option to detect PDAC.
authors.affiliation: From the *Department of General and Visceral Surgery, †Gerhard-Domagk Institute of Pathology, and ‡Comprehensive Cancer Center Muenster, University Hospital of Muenster Albert-Schweitzer-Campus 1, Muenster, Germany.
authors.forename: Wolf Arif
authors.initials: WA
authors.lastname: Mardin
authors.forename: Dimitris
authors.initials: D
authors.lastname: Ntalos
authors.forename: Soeren Torge
authors.initials: ST
authors.lastname: Mees
authors.forename: Tilmann
authors.initials: T
authors.lastname: Spieker
authors.forename: Norbert
authors.initials: N
authors.lastname: Senninger
authors.forename: Joerg
authors.initials: J
authors.lastname: Haier
authors.forename: Sameer A
authors.initials: SA
authors.lastname: Dhayat
mesh_terms: D000818:Animals; D015153:Blotting, Western; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis / Q000235:genetics*; D045744:Cell Line, Tumor; D019175:DNA Methylation; D003937:Diagnosis, Differential; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000235:genetics*; D010195:Pancreatitis / Q000175:diagnosis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D015843:Serpins / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: C085344:SERPIN-B5; D015843:Serpins