title: Proteomic analysis to identify plasma orosomucoid 2 and kinesin 18A as potential biomarkers of cholangiocarcinoma.
abstract: Proteomic analysis was performed to search for the diagnostic biomarkers of the early stage of cholangiocarcinoma (CCA). For this purpose, CCA was experimentally induced in hamsters by the combination of N-nitrosodimethylamine (NDMA) treatment and Opisthorchis viverrini (OV) infection. Pooled plasma of normal control, NDMA-treated, OV-infected and OV+NDMA (ON) treated group was separated by 1-D PAGE, and the trypsin-digested bands were analyzed with LC-MS/MS. Among 82 overexpressed proteins, the study focused on 26 proteins overexpressed in ON group because CCA development was almost exclusively found in this group. A further selection was made based on the protein overexpression on day 21, the precancerous stage. Orosomucoid 2 (Orm2) was overexpressed in OV and ON groups and kinesin 18A (KIF18A) was overexpressed in the ON group. The overexpression levels were verified by real-time RT-PCR and western blotting in the liver and plasma. The transcription and translation levels of these two candidate molecules increased significantly at 21 days post-treatment before tumor development. Immunohistochemistry revealed KIF18A was expressed in the epithelial cells of newly formed small bile ducts, some inflammatory cells and hepatocytes. These results suggest that Orm2 and KIF18A could be the potential biomarkers for early diagnosis of CCA.
authors: Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors: Rucksak
authors: R
authors: Rucksaken
authors: Jarinya
authors: J
authors: Khoontawad
authors: Sittiruk
authors: S
authors: Roytrakul
authors: Porntip
authors: P
authors: Pinlaor
authors: Yusuke
authors: Y
authors: Hiraku
authors: Chaisiri
authors: C
authors: Wongkham
authors: Chawalit
authors: C
authors: Pairojkul
authors: Thidarut
authors: T
authors: Boonmars
authors: Somchai
authors: S
authors: Pinlaor
mesh_terms: D000818:Animals; D001650:Bile Duct Neoplasms / Q000097:blood* / Q000139:chemically induced / Q000469:parasitology; D001653:Bile Ducts, Intrahepatic / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000097:blood*; D018281:Cholangiocarcinoma / Q000097:blood* / Q000139:chemically induced / Q000469:parasitology; D006224:Cricetinae; D004128:Dimethylnitrosamine; D004195:Disease Models, Animal; D008297:Male; D008647:Mesocricetus; D009889:Opisthorchiasis; D009891:Opisthorchis; D009961:Orosomucoid / Q000378:metabolism*; D040901:Proteomics / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor; D009961:Orosomucoid; D004128:Dimethylnitrosamine