title: Overexpression of PDGFA and its receptor during carcinogenesis of Opisthorchis viverrini-associated cholangiocarcinoma.
abstract: Cholangiocarcinoma (CCA) is a crucial health problem in northeastern part of Thailand, which is caused by a combination of Opisthorchis viverrini infection and nitrosamine. A better understanding of its molecular mechanism is an important step to discover and develop the new diagnostics and therapies for CCA. To reveal the involvement of potential genes in the development of CCA, the present study investigated the expression kinetics of platelet-derived growth factor alpha (Pdgfa) and its receptor (Pdgfra) during the tumorigenesis of CCA induced by O. viverrini infection with quantitative RT-PCR, and confirmed the expression with immunohistological staining. The results showed that in the hamster model of opisthorchiasis-associated CCA, the expression of Pdgfa was increased after infection plus N-nitrosodimethylamine (NDMA) administration, reached its peak at 2 months post infection, and remained at the high level until 6 months. Similarly, the expression of Pdgfra was increased time-dependently. The positive immunostaining for PDGFA proteins was observed in the cytoplasm of epithelial tumor cells of hamster CCA. Moreover, the analysis of the expression of these genes in 10 cases of human opisthorchiasis-associated CCA showed that Pdgfa was overexpressed in 80%, and Pdgfra was overexpressed in 40% cases (>3.0 folds, compared with the expressions of adjacent normal tissues). This result suggests that PDGFA is likely involved in the tumorigenesis of opisthorchiasis-associated CCA, and may be a promising candidate biomarker for diagnosis and treatment strategies of CCA.
authors.affiliation: Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Sirintip
authors.initials: S
authors.lastname: Boonjaraspinyo
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Wu
authors.forename: Thidarut
authors.initials: T
authors.lastname: Boonmars
authors.forename: Sasithorn
authors.initials: S
authors.lastname: Kaewkes
authors.forename: Watchalin
authors.initials: W
authors.lastname: Loilome
authors.forename: Paiboon
authors.initials: P
authors.lastname: Sithithaworn
authors.forename: Isao
authors.initials: I
authors.lastname: Nagano
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Puangrat
authors.initials: P
authors.lastname: Yongvanit
authors.forename: Vajarabhongsa
authors.initials: V
authors.lastname: Bhudhisawasdi
mesh_terms: D000818:Animals; D001650:Bile Duct Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000469:parasitology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D018281:Cholangiocarcinoma / Q000139:chemically induced / Q000235:genetics* / Q000469:parasitology / Q000473:pathology; D006224:Cricetinae; D004128:Dimethylnitrosamine; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008647:Mesocricetus; D009889:Opisthorchiasis / Q000150:complications* / Q000469:parasitology / Q000503:physiopathology; D009891:Opisthorchis / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012376:Rodent Diseases / Q000139:chemically induced / Q000469:parasitology / Q000503:physiopathology; D013785:Thailand
chemical_list: D010982:Platelet-Derived Growth Factor; C075278:platelet-derived growth factor A; D020796:Receptor, Platelet-Derived Growth Factor alpha; D004128:Dimethylnitrosamine