title: Expression of aurora kinase A correlates with the Wnt-modulator RACGAP1 in gastric cancer.
abstract: Canonical Wnt signaling is involved in gastric carcinogenesis. The aim of this study was to identify the link between Wnt signaling and aurora kinase A (AURKA), a target for the treatment of gastrointestinal cancers. Publicly available microarray data were used to identify phenotype-specific protein-protein interaction (PPI) subnetworks. The in silico analysis revealed a gastric cancer-specific PPI subnetwork consisting of 2745 proteins and 50,935 interactions. We focused on the link of AURKA to a Wnt-specific interaction module consisting of 92 proteins. There was a direct association of AURKA with Rac GTPase-activating protein 1 (RACGAP1), as well as with CTNBB1 (β-catenin) and CDKN1A as second-order interactors. Differential expression analysis revealed a significant downregulation of both AURKA and RACGAP1 in gastric cancer compared to noncancer controls. Biopsies from a prospective cohort of 56 patients with gastric cancer (32 intestinal type, 24 diffuse type) and 20 noncancer controls were used for validation of the identified targets. The RT-PCR data confirmed a strong correlation of AURKA and RACGAP1 gene expression both in the tumor, the tumor-adjacent and the tumor-distant mucosa. RACGAP1 in the tumor was also associated with CTNBB1 expression, and inversely associated with CDKN1A gene expression. Immunohistochemistry confirmed expression of the RACGAP1 protein in gastric cancer and the tumor-adjacent mucosa. RACGAP1 expression was not associated with tumor stage, grading, Lauren type, Helicobacter pylori infection, or age. In conclusion, AURKA is directly associated with the expression of RACGAP1, a modulator of the canonical Wnt signaling pathway.
authors.affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Leipziger Str. 44, 39120, Magdeburg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Bornschein
authors.affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Leipziger Str. 44, 39120, Magdeburg, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Nielitz
authors.affiliation: Department of Computational Biology, Bering Limited, 80 Third Cross Road, Twickenham, TW2 5EA, United Kingdom.
authors.forename: Ignat
authors.initials: I
authors.lastname: Drozdov
authors.affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Leipziger Str. 44, 39120, Magdeburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Selgrad
authors.affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Leipziger Str. 44, 39120, Magdeburg, Germany.|Department of Molecular Genetics, Medical Laboratory for Clinical Chemistry, Microbiology and Infectious Diseases, Am Neustädter Feld 47, 39124, Magdeburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wex
authors.affiliation: Institute of Pathology, Otto-von-Guericke University, Leipziger Str. 44, 39120, Magdeburg, Germany.
authors.forename: Doerthe
authors.initials: D
authors.lastname: Jechorek
authors.affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Leipziger Str. 44, 39120, Magdeburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Link
authors.affiliation: Institute of Pathology, Otto-von-Guericke University, Leipziger Str. 44, 39120, Magdeburg, Germany.|Institute of Pathology, Klinikum Bayreuth GmbH, Preuschwitzer Str. 101, 95445, Bayreuth, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Vieth
authors.affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Leipziger Str. 44, 39120, Magdeburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Malfertheiner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D064096:Aurora Kinase A / Q000235:genetics* / Q000378:metabolism*; D003198:Computer Simulation; D030541:Databases, Genetic; D015536:Down-Regulation; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D060449:Wnt Signaling Pathway
chemical_list: D020690:GTPase-Activating Proteins; C115995:mgcRacGAP; C576917:AURKA protein, human; D064096:Aurora Kinase A
keywords: AURKA; CDKN1A; RACGAP1; Wnt; gastric cancer