PT - JOURNAL ARTICLE AU - Jarinya Khoontawad AU - Chawalit Pairojkul AU - Rucksak Rucksaken AU - Porntip Pinlaor AU - Chaisiri Wongkham AU - Puangrat Yongvanit AU - Ake Pugkhem AU - Alun Jones AU - Jordan Plieskatt AU - Jeremy Potriquet AU - Jeffery Bethony AU - Somchai Pinlaor AU - Jason Mulvenna TI - Differential protein expression marks the transition from infection with <em>Opisthorchis viverrini</em> to cholangiocarcinoma AID - 10.1101/086645 DP - 2016 Jan 01 TA - bioRxiv PG - 086645 4099 - http://biorxiv.org/content/early/2016/11/09/086645.short 4100 - http://biorxiv.org/content/early/2016/11/09/086645.full AB - Parts of Southeast Asia have the highest incidence of intrahepatic cholangiocarcinoma (CCA) in the world due to infection by the liver fluke Opisthorchis viverrini (Ov). Ov-associated CCA is the culmination of chronic Ov-infection, with the persistent production of the growth factors and cytokines associated with persistent inflammation, which can endure for years in Ov-infected individuals prior to transitioning to CCA. Isobaric labelling and tandem mass spectrometry of liver tissue from a hamster model of CCA was used to compare protein expression profiles from inflammed tissue (Ov-infected but not cancerous) versus cancerous tissue (Ov-induced CCA). Immunohistochemistry and immunoblotting were used to verify dysregulated proteins in the animal model and in human tissue. We identified 154 dysregulated proteins that marked the transition from Ov-infection to Ov-induced CCA, i.e. proteins dysregulated during carcinogenesis but not Ov-infection. The verification of dysregulated proteins in resected liver tissue from humans with Ov-associated CCA showed the numerous parallels in protein dysregulation between human and animal models of Ov-induced CCA. To identify potential circulating markers for CCA, dysregulated proteins were compared to proteins isolated from exosomes secreted by a human CCA cell line (KKU055) and 27 proteins were identified as dysregulated in CCA and present in exosomes. These data form the basis of potential diagnostic biomarkers for human Ov-associated CCA. The profile of protein dysregulation observed during chronic Ov-infection and then in Ov-induced CCA provides insight into the etiology of an infection-induced inflammation-related cancer.CCAcholangiocarcinomaOvOpisthorchis viverriniicNDMAN -nitrosodimethylamineIHCimmunohistochemistryMMTSmethyl methanethiosulfonateTPPTrans Proteomic Pipeline