Coding-noncoding gene expression in intrahepatic cholangiocarcinoma

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Abstract

Recent studies have shown that long noncoding RNAs (lncRNAs) play crucial roles in human cancers. However, the function of lncRNAs and their downstream mechanisms are largely unknown in the molecular pathogenesis of intrahepatic cholangiocarcinoma (ICC). In the present study, we performed transcriptomic profiling of ICC and paired adjacent noncancerous tissues (N) by using lncRNA and messenger RNA (mRNA) microarrays. Quantitative real-time polymerase chain reaction was used to validate the microarray results. We tested for correlations between the expression levels of lncRNAs and target genes. Clinicopathologic characteristics and overall survival were compared using thettest and the Kaplan-Meier method, respectively. A total of 2773 lncRNAs were significantly upregulated in ICC tissues compared with the noncancerous tissues, whereas 2392 lncRNAs were downregulated. Bioinformatic analysis indicated that most of the genes were involved in carcinogenesis, hepatic system diseases, and signal transductions. Positive correlations were found between 4 lncRNA-mRNA pairs (RNA43085 and SULF1, RNA47504 and KDM8, RNA58630 and PCSK6, and RNA40057 and CYP2D6). When the clinicopathologic characteristics were accounted for, the cumulative overall survival rate was found to be associated with low expression levels of CYP2D6 (P= 0.005) and PCSK6 (P= 0.038). Patients with high expression levels of CYP2D6 and RNA40057 had a better prognosis (P= 0.014). Our results suggested that the lncRNA expression profiling in ICC tissues is profoundly different from that in noncancerous tissues. Thus, lncRNA may be a potential diagnostic and prognostic biomarker for ICC. Furthermore, the combined assessment of lncRNA and mRNA expressions might predict the survival of patients with ICC.

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