Abstract
Abstract Introduction: Renal cell carcinoma (RCC) is due to its asymptomatic nature usually diagnosed too late or incidentally during the examination for other indications. There is currently none sufficiently sensitive and reliable biomarker for diagnosis, prediction of the disease development or therapeutic outcome in RCC. Long non-coding RNAs (lncRNAs), RNA molecules regulating gene expression present a group of potential biomarkers as their specific expression profiles have been described in many types of tumors including RCC. Main aim of this study was to analyse global expression profiles of lncRNAs by RNA sequencing, compare them with clinical behaviour of the cancer and to characterize functions of the candidate lncRNAs in vitro. Material and methods: Using next-generation sequencing of RNA from the fresh frozen tissue of 22 patients with RCC we compared expression of lncRNAs in tumor and adjacent non-tumor renal parenchyma. Expression of candidate lncRNAs biomarkers (PVT1, LUCAT1, LINC00982 and SLC16A-AS1) has been validated using qPCR on an independent cohort of 30 patients, results have been statistically evaluated using Mann-Whitney U-test, ROC analysis and were correlated with the clinical stage and Fuhrman grade. Expression of PVT1 was silenced using siRNAs in RCC cell cultures (786-0) and functional characteristics of PVT1 have been studied using MTT test, cell counting and scratch-wound assay. Results: Using the DESeq tool, 1163 deregulated lncRNAs have been identified in patients with RCC when lncRNA profiles of tumors and paired renal parenchyma were compared (538 with increased and 625 with decreased expression levels in tumors). PVT1 (AUC 0,8567, sensitivity 86,67%, specificity 76,67%) and LUCAT1 (AUC 0,7756, sensitivity and specificity 90%) have significantly increased expression and LINC00982 (AUC 0,9578, sensitivity 76,67% and specificity 66,67%) has significantly decreased expression (p < 0,001) also in the validation phase. Statistically significant difference in expression of SLC16A-AS1 has not been observed. Partial effect on migration and proliferation has been observed in PVT1 after the transfection by short interfering RNA. Conclusion: PVT1, LUCAT1 and LINC00982 are a potential diagnostic biomarkers of RCC. Their prognostic potential has not been identified. PVT1 indicated oncogenic functioning in RCC cell lines. This work was supported by Ministry of Health of the Czech Republic, grant nr. NV18-03-00554 and by the Ministry of Education, Youth and Sports of the Czech Republic under the project CEITEC 2020 (LQ1601). All rights reserved. Citation Format: Adela Kubickova, Julia Bohosova, Karolina Trachtova, Jiri Sana, Alexandr Poprach, Michal Stanik, Jan Dolezel, Michal Fedorko, Dalibor Pacik, Marek Svoboda, Ondrej Slaby. Long non-coding RNA PVT1 is a promising diagnostic biomarker with oncogenic functioning in renal cell carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3124.
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