title: Ring finger protein 43 expression is associated with genetic alteration status and poor prognosis among patients with intrahepatic cholangiocarcinoma.
abstract: Ring finger E3 ligases have roles in processes central to maintenance of genomic integrity and cellular homeostasis. Many ring finger E3 ligases are implicated in malignancy. Ring finger protein 43 (RNF43) is a ring finger E3 ligase that negatively regulates the Wnt/β-catenin signaling pathway. RNF43 is frequently mutated in several types of malignancy, including intrahepatic cholangiocarcinoma (ICC). The significance of its expression in ICC has not, however, been reported. We determined RNF43 expression and identified RNF43 polymorphisms in ICC tissues. We also investigated the correlation between RNF43 expression and RNF43 mutation status, RNF43 polymorphisms, clinicopathological features, and prognosis of ICC patients. RNF43 reduced expression in ICC, and the reduction of RNF43 messenger RNA expression was significantly correlated with the presence of rs2257205 and RNF43 somatic mutations, confirming that all RNF43 somatic mutations in ICC are inactivating. Overall survival was worst in patients with down-regulation of RNF43. Univariate and multivariate analyses revealed that RNF43 expression was an independent prognostic factor. There was no statistically significant association between RNF43 messenger RNA and protein expression nor any clinicopathological features or RNF43 polymorphisms. The results imply that RNF43 is down-regulated in ICC and may play a crucial role during development of ICC.
authors.affiliation: School of Biochemistry, Institute of Science, Biochemistry-Electrochemistry Research Unit, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand. Electronic address: chutima.sub@sut.ac.th.
authors.forename: Chutima
authors.initials: C
authors.lastname: Talabnin
authors.affiliation: School of Biochemistry, Institute of Science, Biochemistry-Electrochemistry Research Unit, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand.
authors.forename: Patcharee
authors.initials: P
authors.lastname: Janthavon
authors.affiliation: School of Biochemistry, Institute of Science, Biochemistry-Electrochemistry Research Unit, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand.
authors.forename: Sunisa
authors.initials: S
authors.lastname: Thongsom
authors.affiliation: School of Biochemistry, Institute of Science, Biochemistry-Electrochemistry Research Unit, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand.
authors.forename: Wipa
authors.initials: W
authors.lastname: Suginta
authors.affiliation: School of Pathology, Institute of Medicine, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand.
authors.forename: Krajang
authors.initials: K
authors.lastname: Talabnin
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Sopit
authors.initials: S
authors.lastname: Wongkham
mesh_terms: D001650:Bile Duct Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D018281:Cholangiocarcinoma / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015513:Oncogene Proteins / Q000032:analysis / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D044767:Ubiquitin-Protein Ligases
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D015513:Oncogene Proteins; D012333:RNA, Messenger; C496945:RNF43 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: Intrahepatic cholangiocarcinoma; Polymorphisms; Prognosis; Ring finger protein 43; Somatic mutation