Distinct miRNA signatures associate with subtypes of cholangiocarcinoma from infection with the tumourigenic liver fluke Opisthorchis viverrini

Jordan L. Plieskatt, Gabriel Rinaldi, Yanjun Feng, Jin Peng, Ponlapat Yonglitthipagon, Samantha Easley, Therawach Laha, Chawalit Pairojkul, Vajarabhongsa Bhudhisawasdi, Banchob Sripa, Paul J. Brindley, Jason P. Mulvenna, Jeffrey M. Bethony*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Citations (SciVal)

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), 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.

Original languageEnglish
Pages (from-to)850-858
Number of pages9
JournalJournal of Hepatology
Volume61
Issue number4
DOIs
Publication statusPublished - Oct 2014
Externally publishedYes

Keywords

  • Cholangiocarcinoma
  • Histological grade
  • Intrahepatic cholangiocarcinoma
  • Microarray
  • MicroRNA
  • Opisthorchis viverrini
  • Gene Expression Profiling/methods
  • MicroRNAs/genetics
  • Prognosis
  • Humans
  • Middle Aged
  • Opisthorchis/isolation & purification
  • Male
  • Bile Ducts, Intrahepatic/pathology
  • Animals
  • Neoplasm Grading
  • Bile Duct Neoplasms/etiology
  • Female
  • Cholangiocarcinoma/etiology
  • Opisthorchiasis/complications

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