TY - JOUR
T1 - Distinct miRNA signatures associate with subtypes of cholangiocarcinoma from infection with the tumourigenic liver fluke Opisthorchis viverrini
AU - Plieskatt, Jordan L.
AU - Rinaldi, Gabriel
AU - Feng, Yanjun
AU - Peng, Jin
AU - Yonglitthipagon, Ponlapat
AU - Easley, Samantha
AU - Laha, Therawach
AU - Pairojkul, Chawalit
AU - Bhudhisawasdi, Vajarabhongsa
AU - Sripa, Banchob
AU - Brindley, Paul J.
AU - Mulvenna, Jason P.
AU - Bethony, Jeffrey M.
N1 - Funding Information:
The contents are solely the responsibility of the authors and do not represent the official views of NIAID, NCI, the Katzen Cancer Research Center of the George Washington University, or the NHMRC of Australia. This research was partially supported by awards R01CA155297 (JMB, JPM, and PJB) from the National Cancer Institute , P50AI098639 (BS, JMB, and PJB) from the National Institute of Allergy and Infectious Disease , fellowship support (JPM) and research support (JMB and JPM) from the National Health and Medical Research Council of Australia , and research support from the Dr. Cyrus And Myrtle Katzen Cancer Research Center at the George Washington University (PJB and JMB). JB and JM are funded from the GNT1051627 of the National Health and Medical Research Council of Australia . Microarrays were hybridised and scanned at the Genomics and Epigenomics Shared Resource, Georgetown University Medical Center with the assistance of David Goerlitz. We would like to thank Dr. Norman Lee, GWU for guidance and advice on microarrays.
Funding Information:
This research was partially supported by awards R01CA155297 (JMB, JPM, and PJB) from the National Cancer Institute, P50AI098639 (BS, JMB, and PJB) from the National Institute of Allergy and Infectious Disease, fellowship support (JPM) and research support (JMB and JPM) from the National Health and Medical Research Council of Australia, and research support from the Dr. Cyrus And Myrtle Katzen Cancer Research Center at the George Washington University (PJB and JMB).
Publisher Copyright:
© 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
PY - 2014/10
Y1 - 2014/10
N2 - 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), nontumour 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.
AB - 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), nontumour 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.
KW - Cholangiocarcinoma
KW - Histological grade
KW - Intrahepatic cholangiocarcinoma
KW - Microarray
KW - MicroRNA
KW - Opisthorchis viverrini
KW - Gene Expression Profiling/methods
KW - MicroRNAs/genetics
KW - Prognosis
KW - Humans
KW - Middle Aged
KW - Opisthorchis/isolation & purification
KW - Male
KW - Bile Ducts, Intrahepatic/pathology
KW - Animals
KW - Neoplasm Grading
KW - Bile Duct Neoplasms/etiology
KW - Female
KW - Cholangiocarcinoma/etiology
KW - Opisthorchiasis/complications
UR - http://www.scopus.com/inward/record.url?scp=84926410127&partnerID=8YFLogxK
U2 - 10.1016/j.jhep.2014.05.035
DO - 10.1016/j.jhep.2014.05.035
M3 - Article
C2 - 25017828
AN - SCOPUS:84926410127
SN - 0168-8278
VL - 61
SP - 850
EP - 858
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 4
ER -
