Abstract
206 Background: Cholangiocarcinoma in Thailand and Laos is associated with the liver fluke Opisthorchis viverrini (OV). Molecular differences between OV-CCA and Non-OV CCA remain to be defined. MiRNAs are regulators of mRNA that result in transcriptional repression or gene silencing. MiRNA profiles of OV vs. non-OV CCA have not yet been studied. Methods: 50 OV-CCA and 16 non-OV CCA pathological samples were obtained from Liver Fluke and Cholangiocarcinoma Center, Khonkaen University, Thailand and University of Texas, MD Anderson Cancer Center (MDACC), USA, respectively. Macrodissected common bile duct samples from MDACC were used as control groups. Global miRNA expression profiling was performed using the miRCURY LNA microRNA Array (Exiqon).qRT-PCR and in situ hybridization (ISH) were used to validate the miRNAs noted to be significant on the microRNA array. Results: Ten samples of OV and non-OV CCA were analyzed for global miRNA expression; 46 were used for validation. MiRNA microarray identified 71 miRNAs that were differentially expressed between OV-CCA and non-OV CCA (p<0.05). Of the 25 miRNAs with increased expression in OV-CCA, miR-141 and miR-200c were highly significant (p<0.01). These were overexpressed in OV-CCA as compared to control bile duct samples. The validation set on qRT-PCR showed significant miR-200c overexpression in 12 OV-CCA samples (p=0.02) and under expression in four non-OV CCA samples (p=0.006). ISH demonstrated miR-200c overexpression in 32 of 45 (71.1%) OV-CCA samples and 2 of 8 (25%) non-OV CCA samples. There was a trend toward better survival in OV-CCA patients with high miR-200c expression (9.5 vs 5.2 months, p=.08). Conclusions: MiRNA expression profiles differ between OV-CCA and non-OV CCA. MiR-200c was overexpressed in OV-CCA but under expressed in non-OV CCA. MiR-200C is known to repress epithelial-mesenchymal transition and its overexpression in OV-CCA may provide important insight into the distinct pathogenesis and prognosis of OV-CCA.
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