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Characterization of gene expression and activated signaling pathways in solid-pseudopapillary neoplasm of pancreas

 Minhee Park  ;  Minhyung Kim  ;  Daehee Hwang  ;  Misun Park  ;  Won Kyu Kim  ;  Sang Kyum Kim  ;  Jihye Shin  ;  Eun Sung Park  ;  Chang Moo Kang  ;  Young-Ki Paik  ;  Hoguen Kim 
 MODERN PATHOLOGY, Vol.27(4) : 580-593, 2014 
Journal Title
Issue Date
Biomarkers, Tumor/analysis ; Biomarkers, Tumor/genetics* ; Cell Transformation, Neoplastic/genetics ; Cluster Analysis ; Epithelial-Mesenchymal Transition/genetics ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic* ; Gene Regulatory Networks ; Hedgehog Proteins/genetics ; Humans ; MicroRNAs/analysis ; Pancreatic Neoplasms/chemistry ; Pancreatic Neoplasms/genetics* ; Pancreatic Neoplasms/pathology ; RNA, Messenger/analysis ; Receptors, Androgen/genetics ; Reproducibility of Results ; Retrospective Studies ; Signal Transduction/genetics* ; Wnt Signaling Pathway/genetics
Solid-pseudopapillary neoplasm is an uncommon pancreatic tumor with distinct clinicopathologic features. Solid-pseudopapillary neoplasms are characterized by mutations in exon 3 of CTNNB1. However, little is known about the gene and microRNA expression profiles of solid-pseudopapillary neoplasms. Thus, we sought to characterize solid-pseudopapillary neoplasm-specific gene expression and identify the signaling pathways activated in these tumors. Comparisons of gene expression in solid-pseudopapillary neoplasm to pancreatic ductal carcinomas, neuroendocrine tumors, and non-neoplastic pancreatic tissues identified solid-pseudopapillary neoplasm-specific mRNA and microRNA profiles. By analyzing 1686 (1119 upregulated and 567 downregulated) genes differentially expressed in solid-pseudopapillary neoplasm, we found that the Wnt/β-catenin, Hedgehog, and androgen receptor signaling pathways, as well as genes involved in epithelial mesenchymal transition, are activated in solid-pseudopapillary neoplasms. We validated these results experimentally by assessing the expression of β-catenin, WIF-1, GLI2, androgen receptor, and epithelial–mesenchymal transition-related markers with western blotting and immunohistochemistry. Our analysis also revealed 17 microRNAs, especially the miR-200 family and miR-192/215, closely associated with the upregulated genes associated with the three pathways activated in solid-pseudopapillary neoplasm and epithelial mesenchymal transition. Our results provide insight into the molecular mechanisms underlying solid-pseudopapillary neoplasm tumorigenesis and its characteristic less epithelial cell differentiation than the other common pancreatic tumors.
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1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Institute for Medical Convergence (연의-생공연 메디컬융합연구소) > 1. Journal Papers
Yonsei Authors
Kang, Chang Moo(강창무) ORCID logo https://orcid.org/0000-0002-5382-4658
Kim, Won Kyu(김원규)
Kim, Ho Keun(김호근)
Park, Min Hee(박민희)
Park, Eun Sung(박은성)
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