title: Gene expression signature of advanced pancreatic ductal adenocarcinoma using low density array on endoscopic ultrasound-guided fine needle aspiration samples.
abstract: OBJECTIVE
  The purpose of this study was to investigate the clinical feasibility and utility of low-density array analysis on samples obtained from endoscopic ultrasound-guided fine needle aspiration biopsy in locally advanced and/or metastatic pancreatic ductal adenocarcinoma and chronic pancreatitis.
  
  
  METHODS
  In this prospective multicenter study, we quantified candidate gene expression in biopsies sampled from 44 locally advanced and/or metastatic pancreatic carcinoma and from 17 pseudotumoural chronic pancreatitis using dedicated low-density array microfluidic plates.
  
  
  RESULTS
  We first demonstrated that 18S gene expression is stable and comparable in normal pancreas and pancreatic cancer tissues. Next, we found that eight genes (S100P, PLAT, PLAU, MSLN, MMP-11, MMP-7, KRT7, KRT17) were significantly over expressed in pancreatic cancer samples when compared to pseudotumoural chronic pancreatitis (p value ranging from 0.0007 to 0.0215): Linear discriminative analysis identified S100P, PLAT, MSLN, MMP-7, KRT7 as highly explicative variables. The area under receiver operating curve establishes the clinical validity of the potential diagnostic markers identified in this study (values ranging from 0.69 to 0.76). In addition, combination of S100P and KRT7 gave better diagnosis performances (Area Under Receiver Operating Curve 0.81, sensitivity 81%, specificity 77%).
  
  
  CONCLUSIONS
  We demonstrate that molecular studies on EUS-guided FNA material are feasible for the identification and quantification of markers in PDAC patients diagnosed with non-resectable tumours. Using low-density array, we isolated a molecular signature of advanced pancreatic carcinoma including mostly cancer invasion-related genes. This work stems for the use of novel biomarkers for the molecular diagnosis of patient with solid pancreatic masses.
authors.affiliation: INSERM UMR1037, Cancer Research Center of Toulouse, CHU Rangueil, 1 avenue Jean Poulhès, Bât. L3, BP 84225, 31432 Toulouse Cedex 4, France3
authors.forename: B
authors.initials: B
authors.lastname: Bournet
authors.forename: A
authors.initials: A
authors.lastname: Pointreau
authors.forename: A
authors.initials: A
authors.lastname: Souque
authors.forename: N
authors.initials: N
authors.lastname: Oumouhou
authors.forename: F
authors.initials: F
authors.lastname: Muscari
authors.forename: B
authors.initials: B
authors.lastname: Lepage
authors.forename: P
authors.initials: P
authors.lastname: Senesse
authors.forename: M
authors.initials: M
authors.lastname: Barthet
authors.forename: N
authors.initials: N
authors.lastname: Lesavre
authors.forename: P
authors.initials: P
authors.lastname: Hammel
authors.forename: P
authors.initials: P
authors.lastname: Levy
authors.forename: P
authors.initials: P
authors.lastname: Ruszniewski
authors.forename: P
authors.initials: P
authors.lastname: Cordelier
authors.forename: L
authors.initials: L
authors.lastname: Buscail
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D044963:Biopsy, Fine-Needle; D021441:Carcinoma, Pancreatic Ductal / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D019160:Endosonography; D020869:Gene Expression Profiling; D006801:Humans; D000090204:Mesothelin; D010179:Pancreas / Q000000981:diagnostic imaging; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D050500:Pancreatitis, Chronic; D011446:Prospective Studies; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; C000715527:MSLN protein, human; D000090204:Mesothelin