Global profiling of microRNA expression in brain metastases

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F21%3A00074517" target="_blank" >RIV/65269705:_____/21:00074517 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14110/21:00120189

Výsledek na webu

<a href="http://rimononline.in.ua/neurosurgery2021/eng#rec326396620" target="_blank" >http://rimononline.in.ua/neurosurgery2021/eng#rec326396620</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Global profiling of microRNA expression in brain metastases

Popis výsledku v původním jazyce

Background: Brain metastases (BM) are the most common intracranial tumors occurring in 20-40% of adult cancer patients. BM have long received little attention and, in general, symptomatic palliative care has been indicated without attempting to significantly prolong overall survival (OS). The current approach to BM treatment is changing as the incidence increases over time because of more effective treatment of primary tumors prolonging OS, as well as improved imaging to detect smaller asymptomatic BM. Although the survival of patients with BM is generally unfavorable, the prognosis individually varies significantly. Therefore, it would be useful to strengthen prognostic tools with new high-performance molecular markers. Particularly promising are microRNAs (miRNAs), non-coding RNAs with the length of 18-25 nt, which post-transcriptionally regulate gene expression by silencing mRNA targets. They are stable and thus suitable for sequencing and retrospective analyses in FFPE tissues. Although dysregulated expression (DE) and diagnostic potential of miRNAs have been described in tumors, including BM, there is only a handful of studies describing global miRNA expression profiling in BM and their association with OS. Material and methods: Sequencing of fresh-frozen histopathologically confirmed 71 BM tissues (lung ca - 37%, melanoma - 23%, breast ca - 18%, RCC - 15%, CRC - 7%) was performed. Informed consent approved by the local ethics committee was obtained from patients prior to treatment. A panel of 2437 mature miRNAs was evaluated statistically. The miraligner was used for mapping the reads to the reference genome and the sum of the reads per target sequence, and limma was used for the differential expression analysis. Results: Differential analysis revealed 373 miRNAs with significantly DE in 5 BM groups (p &lt;0.001). Unsupervised clustering analysis based on the expression of 58 miRNAs was able to correctly classify 42% BM of lung ca, 81% BM of melanoma, 85% BM of breast ca, 82% BM of RCC and 100% BM of CRC. MiR-200c-3p, miR-141-5p, miR-141-3p, miR-200c-5p, miR-215-5p, miR-200b-3p, miR-211-3p, miR-429, miR-200a-3p and miR-200b-5p were selected for validation. Conclusion: These results confirmed significantly DE of miRNAs in BM, which may serve as suitable diagnostic markers in BM. The results will be verified in an independent set of FFPE tissues and statistically analyzed in connection with OS and prognostic scoring systems.

Název v anglickém jazyce

Global profiling of microRNA expression in brain metastases

Popis výsledku anglicky

Background: Brain metastases (BM) are the most common intracranial tumors occurring in 20-40% of adult cancer patients. BM have long received little attention and, in general, symptomatic palliative care has been indicated without attempting to significantly prolong overall survival (OS). The current approach to BM treatment is changing as the incidence increases over time because of more effective treatment of primary tumors prolonging OS, as well as improved imaging to detect smaller asymptomatic BM. Although the survival of patients with BM is generally unfavorable, the prognosis individually varies significantly. Therefore, it would be useful to strengthen prognostic tools with new high-performance molecular markers. Particularly promising are microRNAs (miRNAs), non-coding RNAs with the length of 18-25 nt, which post-transcriptionally regulate gene expression by silencing mRNA targets. They are stable and thus suitable for sequencing and retrospective analyses in FFPE tissues. Although dysregulated expression (DE) and diagnostic potential of miRNAs have been described in tumors, including BM, there is only a handful of studies describing global miRNA expression profiling in BM and their association with OS. Material and methods: Sequencing of fresh-frozen histopathologically confirmed 71 BM tissues (lung ca - 37%, melanoma - 23%, breast ca - 18%, RCC - 15%, CRC - 7%) was performed. Informed consent approved by the local ethics committee was obtained from patients prior to treatment. A panel of 2437 mature miRNAs was evaluated statistically. The miraligner was used for mapping the reads to the reference genome and the sum of the reads per target sequence, and limma was used for the differential expression analysis. Results: Differential analysis revealed 373 miRNAs with significantly DE in 5 BM groups (p &lt;0.001). Unsupervised clustering analysis based on the expression of 58 miRNAs was able to correctly classify 42% BM of lung ca, 81% BM of melanoma, 85% BM of breast ca, 82% BM of RCC and 100% BM of CRC. MiR-200c-3p, miR-141-5p, miR-141-3p, miR-200c-5p, miR-215-5p, miR-200b-3p, miR-211-3p, miR-429, miR-200a-3p and miR-200b-5p were selected for validation. Conclusion: These results confirmed significantly DE of miRNAs in BM, which may serve as suitable diagnostic markers in BM. The results will be verified in an independent set of FFPE tissues and statistically analyzed in connection with OS and prognostic scoring systems.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

<a href="/cs/project/NV18-03-00398" target="_blank" >NV18-03-00398: Rozšíření současných prognostických skórovacích systémů u mozkových metastáz o mikroRNA profilování s cílem individualizace pooperační péče</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

2021

Kód důvěrnosti údajů

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