Specific lncRNA Expression Patterns in Glioblastoma Subgroups in 80 Cases

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F19%3A00071139" target="_blank" >RIV/65269705:_____/19:00071139 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.nature.com/articles/s41379-019-0232-x.pdf" target="_blank" >https://www.nature.com/articles/s41379-019-0232-x.pdf</a>

DOI - Digital Object Identifier

—

Jazyk výsledku

angličtina

Název v původním jazyce

Specific lncRNA Expression Patterns in Glioblastoma Subgroups in 80 Cases

Popis výsledku v původním jazyce

Background: Glioblastoma (GB) is the most common primary brain tumor of astrocytic origin characterized by an infaust prognosis with the median overall survival (OS) of 13 months. However, survival varies among individual cases. Identification of new prognostic and predictive biomarkers would enable more precise classification of patients according prognosis and therapy response, respectively. Long non-coding RNAs (lncRNAs) are regulators of gene expression playing important roles in the molecular pathology of GB indicating their potential role as biomarkers. Design: Our study included 80 GB patients who underwent standard therapeutic protocol including surgical resection followed by the concomitant chemoradiotherapy with temozolomide and 16 patients with intractable epilepsy. Informed consent approved by the local Ethical Commission was obtained from each patient. MGMT methylation status as well as IDH1 mutation status were evaluated in all GBs. RNA from all tumor and brain non-tumor tissue specimens was extracted and used for next-generation RNA sequencing (RNAseq). rRNA depletion and cDNA library preparation were performed with RiboCop rRNA Depletion Kit V1.2 (Lexogen) and NEBNext Ultra II Directional RNA Library Prep Kit for Illumina (NEB), respectively. RNAseq was done using NextSeq 500 High Output Kit and NextSeq 500 instrument (both Illumina). In total, 8 414 lncRNAs and 24 087 protein-coding RNAs with non-zero RPKM at least in one sample were detected and statistically analyzed. CLC genomic workbench was used for the alignment and target counts. Results: Statistical analysis revealed 84 (p &lt; 0.001) lncRNAs and 24 protein-coding RNAs (P &lt; 1*10-6) deregulated in GB tissues in comparison with control samples. Moreover, 35 lncRNAs showed specific expression pattern in GM patients subgroup with methylated MGMT promoter (P &lt; 0.01). Similarly, 60 lncRNAs were significantly (P &lt; 0.001) deregulated between IDH1 wild-type and mutated GB samples. Finally, 6 lncRNA signature was able to identify patients with worse prognosis (OS &lt; 6 months). Conclusions: We described deregulation of lncRNAs and protein-coding RNAs in GB tissue in comparison with non-tumor brain tissue and specific lncRNA patterns associated with MGMT methylation and IDH1 mutation status. We also identified 6 lncRNA signature allowing stratification of GB patients according their prognosis.

Název v anglickém jazyce

Specific lncRNA Expression Patterns in Glioblastoma Subgroups in 80 Cases

Popis výsledku anglicky

Background: Glioblastoma (GB) is the most common primary brain tumor of astrocytic origin characterized by an infaust prognosis with the median overall survival (OS) of 13 months. However, survival varies among individual cases. Identification of new prognostic and predictive biomarkers would enable more precise classification of patients according prognosis and therapy response, respectively. Long non-coding RNAs (lncRNAs) are regulators of gene expression playing important roles in the molecular pathology of GB indicating their potential role as biomarkers. Design: Our study included 80 GB patients who underwent standard therapeutic protocol including surgical resection followed by the concomitant chemoradiotherapy with temozolomide and 16 patients with intractable epilepsy. Informed consent approved by the local Ethical Commission was obtained from each patient. MGMT methylation status as well as IDH1 mutation status were evaluated in all GBs. RNA from all tumor and brain non-tumor tissue specimens was extracted and used for next-generation RNA sequencing (RNAseq). rRNA depletion and cDNA library preparation were performed with RiboCop rRNA Depletion Kit V1.2 (Lexogen) and NEBNext Ultra II Directional RNA Library Prep Kit for Illumina (NEB), respectively. RNAseq was done using NextSeq 500 High Output Kit and NextSeq 500 instrument (both Illumina). In total, 8 414 lncRNAs and 24 087 protein-coding RNAs with non-zero RPKM at least in one sample were detected and statistically analyzed. CLC genomic workbench was used for the alignment and target counts. Results: Statistical analysis revealed 84 (p &lt; 0.001) lncRNAs and 24 protein-coding RNAs (P &lt; 1*10-6) deregulated in GB tissues in comparison with control samples. Moreover, 35 lncRNAs showed specific expression pattern in GM patients subgroup with methylated MGMT promoter (P &lt; 0.01). Similarly, 60 lncRNAs were significantly (P &lt; 0.001) deregulated between IDH1 wild-type and mutated GB samples. Finally, 6 lncRNA signature was able to identify patients with worse prognosis (OS &lt; 6 months). Conclusions: We described deregulation of lncRNAs and protein-coding RNAs in GB tissue in comparison with non-tumor brain tissue and specific lncRNA patterns associated with MGMT methylation and IDH1 mutation status. We also identified 6 lncRNA signature allowing stratification of GB patients according their prognosis.

Druh

O - Ostatní výsledky

CEP obor

—

OECD FORD obor

30109 - Pathology

Projekt

<a href="/cs/project/NV17-32758A" target="_blank" >NV17-32758A: Imunopatologické mechanismy geneze, průběhu a léčebné odpovědi glioblastomu</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů