Panel of potential lncRNA biomarkers can distinguish various types of liver malignant and benign tumors.

Abstract

Liver cancers are among the deadliest malignancies due to alimited efficacy ofearly diagnostics,the lack of appropriate biomarkers and insufficient discrimination of different types of tumors by classic and molecular methods. In this study, we searched for novel long non-coding RNA (lncRNA) as well as validated several known candidates suitable as probable biomarkers for primary liver tumors of various etiology. We described a novel lncRNA HELIS (aka "HEalthy LIver Specific") and estimated its expression by RT-qPCR in 82 paired tissue samples from patients with hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), combined HCC-CCA, pediatric hepatoblastoma (HBL) and non-malignant hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH). Additionally, we examined expression of cancer-associated lncRNAs HULC, MALAT1, UCA1, CYTOR, LINC01093 and H19, which were previously studied mainly in HCC. We demonstrated that down-regulation of HELIS strongly correlates with carcinogenesis; whereasin tumors with non-hepatocyte origin (HBL, CCA) or in a number of poorly differentiated HCC, this lncRNA is not expressed. We showed that recently discovered LINC01093 is dramatically down-regulated in all malignant liver cancers; while in benign tumors LINC01093 expression is just twice decreased in comparison to adjacent samples. Our study revealed that among all measured biomarkers only down-regulated HELIS and LINC01093, up-regulated CYTOR and dysregulated HULC are perspective for differential diagnostics of liver cancers; whereasothers demonstrated discordant results and cannot be considered as potential universal biomarkers for this purpose.