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 Zatsepin8,6, Maria P Rubtsova8,6, Olga A Dontsova8,6. 1. Center of Life Sciences, Skolkovo Institute of Science and Technology, Skolkovo, Moscow, Russia, 143026. o.burenina@skoltech.ru. 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" of the Ministry of Health of the Russian Federation, Moscow, Russia, 115478. 5. Petrovsky National Research Centre of Surgery, Moscow, Russia, 119991. 6. Lomonosov Moscow State University, Chemistry Department and A.N. Belozersky Institute of Physico-Chemical Biology, Moscow, Russia, 119992. 7. Faculty of Biology and Biotechnologies, Higher School of Economics, Moscow, Russia, 101000. 8. Center of Life Sciences, Skolkovo Institute of Science and Technology, Skolkovo, Moscow, Russia, 143026.
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.
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 tumorsLINC01093 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.
Authors: Miriam Recalde; María Gárate-Rascón; José María Herranz; María Elizalde; María Azkona; Juan P Unfried; Loreto Boix; María Reig; Bruno Sangro; Maite G Fernández-Barrena; Puri Fortes; Matías A Ávila; Carmen Berasain; María Arechederra Journal: Cancers (Basel) Date: 2022-04-19 Impact factor: 6.575