Differential protein expression marks the transition from infection with Opisthorchis viverrinito cholangiocarcinoma

Khoontawad, Jarinya, Pairojkul, Chawalit, Rucksaken, Rucksak, Pinlaor, Porntip, Wongkham, Chaisiri, Yongvanit, Puangrat, Pugkhem, Ake, Jones, Alun, Plieskatt, Jordan, Potriquet, Jeremy, Bethony, Jeffery, Pinlaor, Somchai, and Mulvenna, Jason (2017) Differential protein expression marks the transition from infection with Opisthorchis viverrinito cholangiocarcinoma. Molecular and Cellular Proteomics, 16. pp. 911-923.

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Abstract

Parts of Southeast Asia have the highest incidence of intrahepatic cholangiocarcinoma (CCA) in the world because of 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 labeling and tandem mass spectrometry of liver tissue from a hamster model of CCA was used to compare protein expression profiles from inflammed tissue (Ovinfected 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 with 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 Ovinfection and then in Ov-induced CCA provides insight into the etiology of an infection-induced inflammation-related cancer.

Item ID: 54240
Item Type: Article (Refereed Research - C1)
ISSN: 1535-9484
Funders: National Cancer Institute (NCI), National Institute of Allergy and Infectious Disease (NIAID), National Health and Medical Research Council of Australia (NHMRC)
Projects and Grants: NCI P50AI0986, NHMRC grant 1051627
Date Deposited: 21 Jun 2018 00:27
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110802 Medical Infection Agents (incl Prions) @ 70%
11 MEDICAL AND HEALTH SCIENCES > 1112 Oncology and Carcinogenesis > 111299 Oncology and Carcinogenesis not elsewhere classified @ 30%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920199 Clinical Health (Organs, Diseases and Abnormal Conditions) not elsewhere classified @ 100%
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