Panel of potential lncRNA biomarkers can distinguish various types of liver malignant and benign tumors
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ORIGINAL ARTICLE – CANCER RESEARCH
Panel of potential lncRNA biomarkers can distinguish various types of liver malignant and benign tumors Olga Y. Burenina1 · Natalia L. Lazarevich2,3 · Inna F. Kustova2 · Daria A. Shavochkina2 · Ekaterina A. Moroz4 · Nikolay E. Kudashkin4 · Yuriy I. Patyutko4 · Alexey V. Metelin5 · Eduard F. Kim5 · Dmitry A. Skvortsov6,7 · Timofei S. Zatsepin1,6 · Maria P. Rubtsova1,6 · Olga A. Dontsova1,6 Received: 1 May 2020 / Accepted: 1 September 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
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 HCCCCA, 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, upregulated 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. Keywords LncRNA · Liver cancer · Biomarkers · Hepatocellular carcinoma · Cholangiocarcinoma · Hepatoblastoma
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00432-020-03378-5) contains supplementary material, which is available to authorized users. * Olga Y. Burenina [email protected] 1
Center of Life Sciences, Skolkovo Institute of Science and Technology, Skolkovo, Moscow, Russia 143026
2
Institute of Carcinogenesis, FSBI “N.N. Blokhin National Medical Research Center of Oncology” of the Ministry of Health of the Russian Federation, Moscow, Russia 115478
3
Biology Department, Lomonosov Moscow State University, Moscow, Russia 119234
4
Institute of Clinical Oncology, FSBI “N.N. Blokhin National Medical Research Center of Oncology”
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