Abstract
Purpose
Liver cancers are among the deadliest malignancies due to a limited efficacy of early 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.
Methods
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.
Results
We demonstrated that down-regulation of HELIS strongly correlates with carcinogenesis; whereas in 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.
Conclusion
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; whereas others demonstrated discordant results and cannot be considered as potential universal biomarkers for this purpose.
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Funding
This study was funded by Russian Science Foundation (RSF) grant №18-74-00120 for O.Y.B.
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OYB: performed experiments, analyzed and interpreted the data and wrote initial draft; NLL: analyzed data and participated in the manuscript writing; IFK: performed some initial experiments; DASh, DASk.: collected and characterized samples; EAM: performed histopathological analysis of samples; NEK, YIP, AVM, EFK: performed surgery, collection of tissue samples and monitored outcome of patients; TSZ: provided conceptual advice and wrote the manuscript; MPR, OAD: designed research and wrote the manuscript. We confirm that the manuscript has been read and approved by all named authors, and the order of authors listed in the manuscript is accepted by all of us.
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We confirm that all experiments involving human liver samples were approved by medical ethics committee of our institutions. All procedures were performed in accordance with Declaration of Helsinki (1964) and its later amendments (World Medical Association, 2013).
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Burenina, O.Y., Lazarevich, N.L., Kustova, I.F. et al. Panel of potential lncRNA biomarkers can distinguish various types of liver malignant and benign tumors. J Cancer Res Clin Oncol 147, 49–59 (2021). https://doi.org/10.1007/s00432-020-03378-5
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DOI: https://doi.org/10.1007/s00432-020-03378-5