title: Oxidized alpha-1 antitrypsin as a predictive risk marker of opisthorchiasis-associated cholangiocarcinoma.
abstract: The oxidized alpha-1 antitrypsin (ox-A1AT) is one modified form of A1AT, generated via oxidation at its active site by free radicals released from inflammatory cells which subsequently are unable to inhibit protease enzymes. The presence of ox-A1AT in human serum has been used as oxidative stress indicator in many diseases. As oxidative/nitrative damage is one major contributor in opisthorchiasis-driven cholangiocarcinogenesis, we determined A1AT and ox-A1AT expression in human cholangiocarcinoma (CCA) tissue using immunohistochemical staining and measured serum ox-A1AT levels by ELISA. A1AT and ox-A1AT were found to be expressed in the tumor of CCA patients. The group with high expression has a significant poor prognosis. Serum levels of ox-A1AT were also significantly higher in groups of patients with heavy Opisthorchis viverrini infection, advanced periductal fibrosis (APF) and CCA when compared with healthy controls (P < 0.001). Odds ratio (OR) analysis implicated high ox-A1AT levels as a risk predictor for APF and CCA (P < 0.001; OR = 140.5 and 22.0, respectively). In conclusion, as APF may lead to hepatobiliary diseases and an increased risk of CCA development, our results identified ox-A1AT as a potential risk indicator for opisthorchiasis-associated CCA. This marker could now be explored for screening of subjects living in endemic areas where the prevalence of opisthorchiasis still remains high.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
authors.forename: Wassana
authors.initials: W
authors.lastname: Jamnongkan
authors.forename: Anchalee
authors.initials: A
authors.lastname: Techasen
authors.forename: Raynoo
authors.initials: R
authors.lastname: Thanan
authors.forename: Kunyarat
authors.initials: K
authors.lastname: Duenngai
authors.forename: Paiboon
authors.initials: P
authors.lastname: Sithithaworn
authors.forename: Eimorn
authors.initials: E
authors.lastname: Mairiang
authors.forename: Watcharin
authors.initials: W
authors.lastname: Loilome
authors.forename: Nisana
authors.initials: N
authors.lastname: Namwat
authors.forename: Chawalit
authors.initials: C
authors.lastname: Pairojkul
authors.forename: Puangrat
authors.initials: P
authors.lastname: Yongvanit
mesh_terms: D000328:Adult; D000818:Animals; D001650:Bile Duct Neoplasms / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D016022:Case-Control Studies; D018281:Cholangiocarcinoma / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009889:Opisthorchiasis / Q000150:complications* / Q000469:parasitology; D009891:Opisthorchis / Q000472:pathogenicity; D010084:Oxidation-Reduction; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult; D000515:alpha 1-Antitrypsin / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D000515:alpha 1-Antitrypsin