title: MicroRNA profiling in periampullary carcinoma.
abstract: BACKGROUND
  MicroRNA expression patterns in many physiological and oncogenic processes have been established. However, the role of aberrant miRNA expression in periampullary carcinoma (PAC) has not been elucidated. We hypothesize that PAC may have differential expression of miRNAs which may differentiate the tumor histological subtypes.
  
  
  METHODS
  Fresh paired tumor and control samples were collected from the PAC patients undergoing Whipple's pancreaticoduodenectomy. Microarray miRNA profiling was performed utilizing tumor (n = 40) and control tissues; adjacent normal pancreas (n = 22), six each distal CBD, duodenum and ampulla. Data obtained was subjected to statistical and bioinformatic analysis. Differentially expressed miRNAs obtained were validated using qPCR in an independent set of samples.
  
  
  RESULTS
  Comparison of PAC tissue samples with controls revealed 29 common and differentially expressed miRNAs (20 upregulated and 9 downregulated) with a higher statistical significance (p < 0.001) and fold change (log2 FC > 1.5). A subset of 16 miRNAs (15 overexpressed and 1 underexpressed) differed in expression levels between pancreatobiliary and intestinal subtypes. Among these, miR-375, miR-31 and miR-196a expressions varied significantly between histological subtypes. Differential expression profiles of miRNAs specific to TNM staging was also observed in PAC subtypes. Target gene prediction for the differentially expressed miRNAs in PAC revealed that target genes are enriched for certain pathways. Particularly, Wnt signaling pathway genes appear to be relevant targets for most of the differentially expressed miRNAs.
  
  
  CONCLUSIONS
  Differentially expressed common miRNA signatures identified in PAC subgroups may have a role in pathogenesis of PAC and miR-375, miR-31 and miR-196a expression patterns may differentiate PAC subtypes.
authors.affiliation: Asian Healthcare Foundation, Hyderabad, India.
authors.forename: Uma Mahesh
authors.initials: UM
authors.lastname: Kalluri Sai Shiva
authors.affiliation: Asian Healthcare Foundation, Hyderabad, India.
authors.forename: Murali Manohar
authors.initials: MM
authors.lastname: Kuruva
authors.affiliation: Asian Healthcare Foundation, Hyderabad, India.
authors.forename: Sasikala
authors.initials: S
authors.lastname: Mitnala
authors.affiliation: Asian Healthcare Foundation, Hyderabad, India; Asian Institute of Gastroenterology, 6-3-661, Somajiguda, Hyderabad 500082, India.
authors.forename: Talukdar
authors.initials: T
authors.lastname: Rupjyoti
authors.affiliation: Asian Institute of Gastroenterology, 6-3-661, Somajiguda, Hyderabad 500082, India.
authors.forename: Rao
authors.initials: R
authors.lastname: Guduru Venkat
authors.affiliation: Asian Healthcare Foundation, Hyderabad, India.
authors.forename: Spandana
authors.initials: S
authors.lastname: Botlagunta
authors.affiliation: Asian Institute of Gastroenterology, 6-3-661, Somajiguda, Hyderabad 500082, India.
authors.forename: Rajasekhar
authors.initials: R
authors.lastname: Kandagaddala
authors.affiliation: Asian Healthcare Foundation, Hyderabad, India.
authors.forename: Siva Prasad
authors.initials: SP
authors.lastname: Siddapuram
authors.affiliation: Asian Institute of Gastroenterology, 6-3-661, Somajiguda, Hyderabad 500082, India.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Sekaran
authors.affiliation: Asian Healthcare Foundation, Hyderabad, India.
authors.forename: Ramji
authors.initials: R
authors.lastname: Chemalakonda
authors.affiliation: Asian Institute of Gastroenterology, 6-3-661, Somajiguda, Hyderabad 500082, India.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Rebala
authors.affiliation: Asian Institute of Gastroenterology, 6-3-661, Somajiguda, Hyderabad 500082, India. Electronic address: aigindia@yahoo.co.in.
authors.forename: Nageshwar Reddy
authors.initials: NR
authors.lastname: Duvvuru
mesh_terms: D014670:Ampulla of Vater / Q000737:chemistry*; D014408:Biomarkers, Tumor / Q000235:genetics; D002277:Carcinoma / Q000235:genetics; D003138:Common Bile Duct Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000032:analysis* / Q000096:biosynthesis; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; C542543:MIRN196 microRNA, human; C534612:MIRN31 microRNA, human; C540933:MIRN375 microRNA, human; D035683:MicroRNAs
keywords: Intestinal subtype; Microarray; Pancreatobiliary; Periampullary carcinoma; miRNAs