Integrated mRNA and lncRNA expression profiling for exploring metastatic biomarkers of human intrahepatic cholangiocarcinoma

摘要

Long noncoding RNAs (lncRNAs) is crucial for various human cancers, but the function and mechanism of lncRNAs is largely unknown in human intrahepatic cholangiocarcinoma (ICC), the second most common liver cancer. In this study, we performed transcriptomic profiling of ICC and normal tissues, and found 2148 lncRNAs and 474 mRNAs were significantly upregulated, whereas 568 lncRNAs and 409 mRNAs were downregulated in ICC tissues. Enrichment analysis suggests these differentially expressed genes mainly focus on response to stimulus, development, and cell proliferation. Further, potential lncRNAs involved in five signaling pathways (ERBB, JAK/STAT, MAPK, VEGF and WNT) were constructed by highly co-expressed with mRNAs in these signaling pathways. The differentially expressed lncRNA-mRNA co-regulated signaling pathways in ICC were further confirmed by lncRNA target prediction. Finally, the differentially expressed lncRNAs were confirmed by quantitative real-time PCR in 32 paired ICC and adjacent tissues. The correlation analysis between the expression levels of lncRNAs and clinicopathologic characteristics showed that EMP1-008, ATF3-008, and RCOR3-013 were observed significantly downregulated in ICC with tumor metastasis. These findings suggested that lncRNA expression profiling in ICC is profoundly different from that in noncancerous tissues, and lncRNA may be used as a potential diagnostic and prognostic biomarker for ICC metastasis.