Project description:The proteomic content of the extracellular vesicles (EVs) released by the liver fluke Opisthorchis viverrini has been addressed in the past, but they have focused on the small population pelleting at 120k vesicles (also named exosomes). Here we provide the first proteomic analysis of vesicles pelleting at 15k (microvesicles) using LC-MS/MS.
Project description:The proteomic content of the extracellular vesicles (EVs) released by the liver fluke Opisthorchis viverrini has been addressed in the past. Here we employ a more comprehensive purification method of the 120k subpopulation of EVs and analyze proteins present in different locations of these EVs (including external trypsin-liberated peptides, cargo proteins and membrane proteins) using LC-MS/MS.
Project description:The impact of different carcinogenic exposures on the specific patterns of somatic mutations in human tumors remains unclear. To clarify this issue, we profiled 209 cholangiocarcinomas (CCAs) from Asia and Europe, including 108 cases caused by liver fluke Opisthorchis viverrini (OV)-infection and 101 cases due to non-OV etiologies. Whole-exome (N = 15) and prevalence screening (N = 194) revealed recurrent somatic mutations in BAP1 and ARID1A, neither of which has been previously reported to be mutated in CCA. Comparisons between intrahepatic OV and non-OV CCAs demonstrated statistically significant different mutation patterns: BAP1 and IDH1/2 were more frequently mutated in non-OV CCAs, while TP53 displayed the reciprocal pattern. Functional studies demonstrated tumor suppressive roles of BAP1 and ARID1A, establishing the role of chromatin modulators in CCA pathogenesis. These findings indicate that different causative etiologies may induce distinct somatic alterations even within the same tumor type.
Project description:The impact of different carcinogenic exposures on the specific patterns of somatic mutations in human tumors remains unclear. To clarify this issue, we profiled 209 cholangiocarcinomas (CCAs) from Asia and Europe, including 108 cases caused by liver fluke Opisthorchis viverrini (OV)-infection and 101 cases due to non-OV etiologies. Whole-exome (N = 15) and prevalence screening (N = 194) revealed recurrent somatic mutations in BAP1 and ARID1A, neither of which has been previously reported to be mutated in CCA. Comparisons between intrahepatic OV and non-OV CCAs demonstrated statistically significant different mutation patterns: BAP1 and IDH1/2 were more frequently mutated in non-OV CCAs, while TP53 displayed the reciprocal pattern. Functional studies demonstrated tumor suppressive roles of BAP1 and ARID1A, establishing the role of chromatin modulators in CCA pathogenesis. These findings indicate that different causative etiologies may induce distinct somatic alterations even within the same tumor type.
Project description:O. viverrini infection is recognised by the WHO as a group 1 biological carcinogen because of its extremely strong link with cholangiocarcinoma (CCA), cancer of the bile ducts. The incidence of CCA associated with liver fluke infection, calculated as an age‐standardized rate, varies by geographical region and other risk factors but exceeds 100 per 100,000 in men and 40 per 100,000 in women in hotspots in northeast Thailand. Any attempts to control liver fluke infection, whether through mass drug administration or ultimately through vaccination requires specific and sensitive diagnostic tools that are readily deployable in the field and easy to use. It is imperative that methods to detect infection are appropriately sensitive and rapid in order to diagnose new cases, assess effectiveness of elimination measures and be applicable to large-scale disease surveillance. Indeed, the WHO recently highlighted the low sensitivity of current diagnostic methods as a barrier to controlling liver fluke infection. Herein, we have leveraged the O. viverrini soluble secreted proteome to help create the first O. viverrini protein microarray.
