RT Journal Article
SR Electronic
T1 Differential protein expression marks the transition from infection with <em>Opisthorchis viverrini</em> to cholangiocarcinoma
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 086645
DO 10.1101/086645
A1 Jarinya Khoontawad
A1 Chawalit Pairojkul
A1 Rucksak Rucksaken
A1 Porntip Pinlaor
A1 Chaisiri Wongkham
A1 Puangrat Yongvanit
A1 Ake Pugkhem
A1 Alun Jones
A1 Jordan Plieskatt
A1 Jeremy Potriquet
A1 Jeffery Bethony
A1 Somchai Pinlaor
A1 Jason Mulvenna
YR 2016
UL http://biorxiv.org/content/early/2016/11/09/086645.abstract
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