title: Salivary MicroRNA in Pancreatic Cancer Patients.
abstract: BACKGROUND
  Pancreatic cancer is the fourth leading cause of cancer death in Western countries, with the lowest 1-year survival rate among commonly diagnosed cancers. Reliable biomarkers for pancreatic cancer diagnosis are lacking and are urgently needed to allow for curative surgery. As microRNA (miRNA) recently emerged as candidate biomarkers for this disease, we explored in the present pilot study the differences in salivary microRNA profiles between patients with pancreatic tumors that are not eligible for surgery, precancerous lesions, inflammatory disease or cancer-free patients as a potential early diagnostic tool.
  
  
  METHODS
  Whole saliva samples from patients with pancreatic cancer (n = 7), pancreatitis (n = 4), IPMN (n = 2), or healthy controls (n = 4) were obtained during endoscopic examination. After total RNA isolation, expression of 94 candidate miRNAs was screened by q(RT)PCR using Biomark Fluidgm. Human-derived pancreatic cancer cells were xenografted in athymic mice as an experimental model of pancreatic cancer.
  
  
  RESULTS
  We identified hsa-miR-21, hsa-miR-23a, hsa-miR-23b and miR-29c as being significantly upregulated in saliva of pancreatic cancer patients compared to control, showing sensitivities of 71.4%, 85.7%, 85,7% and 57%, respectively and excellent specificity (100%). Interestingly, hsa-miR-23a and hsa-miR23b are overexpressed in the saliva of patients with pancreatic cancer precursor lesions. We found that hsa-miR-210 and let-7c are overexpressed in the saliva of patients with pancreatitis as compared to the control group, with sensitivity of 100% and 75%, and specificity of 100% and 80%, respectively. Last hsa-miR-216 was upregulated in cancer patients as compared to patients diagnosed with pancreatitis, with sensitivity of 50% and specificity of 100%. In experimental models of PDAC, salivary microRNA detection precedes systemic detection of cancer cells markers.
  
  
  CONCLUSIONS
  Our novel findings indicate that salivary miRNA are discriminatory in pancreatic cancer patients that are not eligible for surgery. In addition, we demonstrate in experimental models that salivary miRNA detection precedes systemic detection of cancer cells markers. This study stems for the use of salivary miRNA as biomarker for the early diagnosis of patients with unresectable pancreatic cancer.
authors.affiliation: Inserm, UMR1037 CRCT, F-31000 Toulouse, France; Université Toulouse III-Paul Sabatier, UMR1037 CRCT, F-31000 Toulouse, France; Department of Surgery, CHU Toulouse- Rangueil, Toulouse, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Humeau
authors.affiliation: Inserm, UMR1037 CRCT, F-31000 Toulouse, France; Université Toulouse III-Paul Sabatier, UMR1037 CRCT, F-31000 Toulouse, France; Department of Gastroenterology, CHU Toulouse- Rangueil, Toulouse, France.
authors.forename: Alix
authors.initials: A
authors.lastname: Vignolle-Vidoni
authors.affiliation: Inserm, UMR1037 CRCT, F-31000 Toulouse, France; Université Toulouse III-Paul Sabatier, UMR1037 CRCT, F-31000 Toulouse, France.
authors.forename: Flavie
authors.initials: F
authors.lastname: Sicard
authors.affiliation: Université Toulouse III-Paul Sabatier, UMR1037 CRCT, F-31000 Toulouse, France; INSERM U1048, F-31000 Toulouse, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Martins
authors.affiliation: Inserm, UMR1037 CRCT, F-31000 Toulouse, France; Université Toulouse III-Paul Sabatier, UMR1037 CRCT, F-31000 Toulouse, France; Department of Gastroenterology, CHU Toulouse- Rangueil, Toulouse, France.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bournet
authors.affiliation: Inserm, UMR1037 CRCT, F-31000 Toulouse, France; Université Toulouse III-Paul Sabatier, UMR1037 CRCT, F-31000 Toulouse, France; Department of Gastroenterology, CHU Toulouse- Rangueil, Toulouse, France.
authors.forename: Louis
authors.initials: L
authors.lastname: Buscail
authors.affiliation: Inserm, UMR1037 CRCT, F-31000 Toulouse, France; Université Toulouse III-Paul Sabatier, UMR1037 CRCT, F-31000 Toulouse, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Torrisani
authors.affiliation: Inserm, UMR1037 CRCT, F-31000 Toulouse, France; Université Toulouse III-Paul Sabatier, UMR1037 CRCT, F-31000 Toulouse, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Cordelier
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012463:Saliva / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D035683:MicroRNAs