title: Plasma hydroxyproline, MMP-7 and collagen I as novel predictive risk markers of hepatobiliary disease-associated cholangiocarcinoma.
abstract: Chronic opisthorchiasis caused by Opisthorchis viverrini infection is characterized by advanced periductal fibrosis leading to hepatobiliary diseases (HBD), including cholangiocarcinoma (CCA). We aimed to determine fibrotic markers to differentiate HBD status including opisthorchiasis, benign biliary disease (BBD) and CCA. Candidate fibrotic markers in plasma of healthy individuals (n = 14) and patients with opisthorchiasis (n = 32, pre- and post-treatment with praziquantel), BBD (n = 31), CCA (n = 37) and other types of tumors (n = 14) were measured by ELISA and zymography. Plasma levels of hydroxyproline (HYP), collagen I, MMP-7 and TIMP2 in opisthorchiasis patients were significantly higher than those in healthy individuals, and MMP9/TIMP2 balance may be associated with tissue resorption after praziquantel treatment. HYP and TIMP-2 levels were significantly correlated with periductal fibrosis status evaluated by ultrasonography. Plasma HYP level of CCA patients was the highest among HBD patients (p < 0.05). ROC curves revealed HYP, MMP-7 and collagen I levels significantly distinguished opisthorchiasis, BBD and CCA (p < 0.001). Odd ratio (OR) analysis demonstrated these markers in opisthorchiasis were predictable for BBD risk (p < 0.05; OR = 28.50, 10.12 and 4.63 for collagen I, MMP-7 and HYP, respectively), and the risk was reduced by praziquantel treatment. Interestingly, only plasma HYP level in BBD was predictable for CCA risk (OR = 3.69; p = 0.020). In conclusion, plasma HYP, collagen I and MMP-7 may be useful as novel predictive markers of opisthorchiasis-related BBD, and HYP may be used as a diagnostic marker for CCA.
authors.affiliation: Department of Parasitology, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Suksanti
authors.initials: S
authors.lastname: Prakobwong
authors.forename: Lakhanawan
authors.initials: L
authors.lastname: Charoensuk
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Hiraku
authors.forename: Porntip
authors.initials: P
authors.lastname: Pinlaor
authors.forename: Chawalit
authors.initials: C
authors.lastname: Pairojkul
authors.forename: Eimorn
authors.initials: E
authors.lastname: Mairiang
authors.forename: Paiboon
authors.initials: P
authors.lastname: Sithithaworn
authors.forename: Puangrat
authors.initials: P
authors.lastname: Yongvanit
authors.forename: Narong
authors.initials: N
authors.lastname: Khuntikeo
authors.forename: Somchai
authors.initials: S
authors.lastname: Pinlaor
mesh_terms: D001650:Bile Duct Neoplasms / Q000097:blood* / Q000150:complications; D001653:Bile Ducts, Intrahepatic / Q000473:pathology*; D001660:Biliary Tract Diseases / Q000150:complications; D015415:Biomarkers / Q000097:blood*; D018281:Cholangiocarcinoma / Q000097:blood* / Q000150:complications; D024042:Collagen Type I / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006909:Hydroxyproline / Q000097:blood*; D057230:Limit of Detection; D008113:Liver Neoplasms / Q000150:complications; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000097:blood*; D012372:ROC Curve
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D020783:Matrix Metalloproteinase 7; D006909:Hydroxyproline