Gene Expression Profiling of Intrahepatic Cholangiocarcinoma

Abstract

Intrahepatic cholangiocarcinoma (ICC) is ranked as one of the top five causes of cancer-related deaths. ICCin Thai patients is associated with infection with the liver fluke, Opisthorchis viverrini, but the molecular basis fordevelopment remains unclear. The present study employed a microarray approach to compare gene expressionprofiles of ICCs and normal liver tissues from the same patients residing in Northeast Thailand, a region witha high prevalence of liver fluke infection. In ICC samples, 2,821 and 1,361 genes were found to be significantlyup- and down-regulated respectively (unpaired t-test, p<0.05; fold-change ≥2.0). For validation of the microarrayresults, 7 up-regulated genes (FXYD3, GPRC5A, CEACAM5, MUC13, EPCAM, TMC5, and EHF) and 3 downregulatedgenes (CPS1, TAT, and ITIH1) were selected for confirmation using quantitative RT-PCR, resultingin 100% agreement. The metallothionine heavy metal pathway contains the highest percentage of genes withstatistically significant changes in expression. This study provides exon-level expression profiles in ICC thatshould be fruitful in identifying novel genetic markers for classifying and possibly early diagnosis of this highlyfatal type of cholangiocarcinoma.