Opisthorchiasis has the significant relationship with the high prevalence of
cholangiocarcinoma (CCA; a
bile duct cancer) in the endemic areas in Southeast Asia. To reveal the molecular mechanism of the
tumorigenesis induced by
Opisthorchis viverrini infection, the present study investigated the kinetic expression of RB pathway genes, including RB1, p16(INK4),
cyclin D1, and CDK4, during the development of
opisthorchiasis-associated CCA in hamster model. The results of quantitative real-time polymerase chain reaction indicated that the expressions of RB1 and p16(INK4) were down-regulated during the development of CCA induced by
infection plus
N-nitrosodimethylamine treatment in a time-dependent manner. On the other hand, the expressions of
cyclin D1 and CDK4 were up-regulated. The expression kinetics was corresponding to the pathological progression of the
opisthorchiasis-associated CCA, revealed by histopathological observation. Moreover, the analysis of the expression of these genes in human
opisthorchiasis-associated CCA cases showed the decreased expression of RB1 and p16(INK4) in 50% and 82.7% cases and overexpression of
cyclin D1 and CDK4 in half cases, respectively. The results suggested that RB pathway is likely involved in the
tumorigenesis of
opisthorchiasis-induced CCA and proposed the potential application of some of these genes as
biomarkers in predispose and molecular
therapy of the parasite-associated
cancer.