Jordan L Plieskatt1, Gabriel Rinaldi2, Yanjun Feng1, Jin Peng1, Ponlapat Yonglitthipagon3, Samantha Easley4, Therawach Laha5, Chawalit Pairojkul6, Vajarabhongsa Bhudhisawasdi6, Banchob Sripa6, Paul J Brindley1, Jason P Mulvenna7, Jeffrey M Bethony8. 1. Department of Microbiology, Immunology & Tropical Medicine, School of Medicine & Health Sciences, The George Washington University, Washington, DC 20037, USA; Research Center for the Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington, DC 20037, USA. 2. Department of Microbiology, Immunology & Tropical Medicine, School of Medicine & Health Sciences, The George Washington University, Washington, DC 20037, USA; Research Center for the Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington, DC 20037, USA; Departamento de Genética, Facultad de Medicina, Universidad de la República (UDELAR), Montevideo 11800, Uruguay. 3. Infectious Disease and Cancer, Queensland Institute for Medical Research, Brisbane, Australia. 4. Department of Pathology, School of Medicine and Health Sciences, George Washington University, Washington, DC, USA. 5. Department of Parasitology, Khon Kaen University School of Medicine, Khon Kaen 40002, Thailand. 6. Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. 7. Infectious Disease and Cancer, Queensland Institute for Medical Research, Brisbane, Australia; School of Biomedical Sciences, Faculty of Medicine and Biomedical Sciences, University of Queensland, Brisbane, Australia. 8. Department of Microbiology, Immunology & Tropical Medicine, School of Medicine & Health Sciences, The George Washington University, Washington, DC 20037, USA; Research Center for the Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington, DC 20037, USA. Electronic address: jbethony@gwu.edu.
Abstract
BACKGROUND & AIMS: Intrahepatic cholangiocarcinoma (ICC) is a significant public health problem in East Asia, where it is strongly associated with chronic infection by the food-borne parasite Opisthorchis viverrini (OV). We report the first comprehensive miRNA expression profiling by microarray of the most common histologic grades and subtypes of ICC: well differentiated, moderately differentiated, and papillary ICC. METHODS: MicroRNA expression profiles from FFPE were compared among the following: ICC tumour tissue (n = 16), non-tumour tissue distally macrodissected from the same ICC tumour block (n = 15), and normal tissue (n = 13) from individuals undergoing gastric bypass surgery. A panel of deregulated miRNAs was validated by qPCR. RESULTS: Each histologic grade and subtype of ICC displayed a distinct miRNA profile, with no cohort of miRNAs emerging as commonly deregulated. Moderately differentiated ICC showed the greatest miRNA deregulation in quantity and magnitude, followed by the papillary subtype, and then well differentiated ICC. Moreover, when ICC tumour tissues were compared to adjacent non-tumour tissue, similar miRNA dysregulation profiles were observed. CONCLUSIONS: We show that common histologic grades and subtypes of ICC have distinct miRNA profiles. As histological grade and subtypes are associated with ICC aggressiveness, these profiles could be used to enhance the early detection and improve the personalised treatment for ICC. These findings also suggest the involvement of specific miRNAs during ICC tumour progression and differentiation. We plan to use these insights to (a) detect these profiles in circulation and (b) conduct functional analyses to decipher the roles of miRNAs in ICC tumour differentiation.
BACKGROUND & AIMS:Intrahepatic cholangiocarcinoma (ICC) is a significant public health problem in East Asia, where it is strongly associated with chronic infection by the food-borne parasite Opisthorchis viverrini (OV). We report the first comprehensive miRNA expression profiling by microarray of the most common histologic grades and subtypes of ICC: well differentiated, moderately differentiated, and papillary ICC. METHODS: MicroRNA expression profiles from FFPE were compared among the following: ICC tumour tissue (n = 16), non-tumour tissue distally macrodissected from the same ICC tumour block (n = 15), and normal tissue (n = 13) from individuals undergoing gastric bypass surgery. A panel of deregulated miRNAs was validated by qPCR. RESULTS: Each histologic grade and subtype of ICC displayed a distinct miRNA profile, with no cohort of miRNAs emerging as commonly deregulated. Moderately differentiated ICC showed the greatest miRNA deregulation in quantity and magnitude, followed by the papillary subtype, and then well differentiated ICC. Moreover, when ICC tumour tissues were compared to adjacent non-tumour tissue, similar miRNA dysregulation profiles were observed. CONCLUSIONS: We show that common histologic grades and subtypes of ICC have distinct miRNA profiles. As histological grade and subtypes are associated with ICC aggressiveness, these profiles could be used to enhance the early detection and improve the personalised treatment for ICC. These findings also suggest the involvement of specific miRNAs during ICC tumour progression and differentiation. We plan to use these insights to (a) detect these profiles in circulation and (b) conduct functional analyses to decipher the roles of miRNAs in ICC tumour differentiation.
Authors: Jin Peng; Yanjun Feng; Gabriel Rinaldi; Ponlapat Yonglitthipagon; Samantha E Easley; Therawach Laha; Chawalit Pairojkul; Vajarabhongsa Bhudhisawasdi; Banchob Sripa; Paul J Brindley; Jason P Mulvenna; Jeffrey M Bethony; Jordan L Plieskatt Journal: Genom Data Date: 2014-08-28
Authors: Anna Yakovleva; Jordan L Plieskatt; Sarah Jensen; Razan Humeida; Jonathan Lang; Guangzhao Li; Paige Bracci; Sylvia Silver; Jeffrey Michael Bethony Journal: PLoS One Date: 2017-07-25 Impact factor: 3.240
Authors: Sonja M Kessler; Eva Lederer; Stephan Laggai; Nicole Golob-Schwarzl; Kevan Hosseini; Johannes Petzold; Caroline Schweiger; Robert Reihs; Marlen Keil; Jens Hoffmann; Christian Mayr; Tobias Kiesslich; Martin Pichler; Kyung Sik Kim; Hyungjin Rhee; Young Nyun Park; Sigurd Lax; Peter Obrist; Alexandra K Kiemer; Johannes Haybaeck Journal: Oncotarget Date: 2017-09-21