BACKGROUND/AIM: Brain metastases (BMs) are the most frequent intracranial tumors in adults and one of the greatest challenges for modern oncology. Most are derived from lung, breast, renal cell, and colorectal carcinomas and melanomas. Up to 14% of patients are diagnosed with BMs of unknown primary, which are commonly characterized by an early and aggressive metastatic spread. It is important to discover novel biomarkers for early identification of BM origin, allowing better management of patients with this disease. Our study focused on microRNAs (miRNAs), which are very stable in frozen native and FFPE tissues and have been shown to be sensitive and specific diagnostic biomarkers of cancer. We aimed to identify miRNAs with significantly different expression in the five most frequent groups of BMs and develop a diagnostic classifier capable of sensitive and specific classification of BMs. MATERIALS AND METHODS: Total RNA enriched for miRNAs was isolated using the mirVana miRNA Isolation Kit from 71 fresh-frozen histopathologically confirmed BM tissues originating in 5 cancer types. Sequencing libraries were prepared using the QIAseq miRNA Library Kit and sequenced on the NextSeq 500 platform. MiRNA expression was further validated by RT-qPCR. RESULTS: Differential analysis identified 373 miRNAs with significantly different expression between 5 BM groups (p<0.001). A classifier model was developed based on the expression of 6 miRNAs (hsa-miR-141-3p, hsa-miR-141-5p, hsa-miR-146a-5p, hsa-miR-194-5p, hsa-miR-200b-3p and hsa-miR-365b-5p) with the ability to correctly classify 91.5% of samples. Subsequent validation confirmed both significantly different expression of selected miRNAs in 5 BM groups as well as their diagnostic potential. CONCLUSION: To date, our study is the first to analyze miRNA expression in various types of BMs using small RNA sequencing to develop a diagnostic classifier and, thus, to help stratify BMs of unknown primary. The presented results confirm the importance of studying the dysregulated expression of miRNAs in BMs and the diagnostic potential of the validated 6-miRNA signature.

• MeSH
• biologické markery MeSH
• dospělí MeSH
• lidé MeSH
• melanom * MeSH
• mikro RNA * genetika   metabolismus   MeSH
• nádory mozku * genetika   MeSH
• nádory neznámé primární lokalizace * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Úvod: Incidence meningeomů po 65. roku života exponenciálně roste. Tento věk je ovšem typický vyšším výskytem komorbidit a benefit operace nemusí být vždy vyšší než její riziko. Optimalizace léčby by proto měla být objektivně posouzena i s využitím skórovacích systémů. Materiál a metodika: Retrospektivní analýzou byla zhodnocena skupina pacientů léčených ve FN Brno v období 2010–2018 (n = 108). Pacienti byli starší 65 let. V léčbě byly uplatňovány tři postupy: strategie „watch and wait“, operace a stereotaktická radiochirurgie. Skupiny pacientů byla vyhodnocena z pohledu výskytu komorbidit a celkového stavu pacienta s ohledem na výběr terapeutické modality. V indikaci k jednotlivým typům léčby se uplatňovaly skórovací systémy. Dále byly v jednotlivých skupinách vyhodnoceny krátkodobá i dlouhodobá morbidita a mortalita. Výsledky: Pozorovali jsme významnou závislost při analýze roční mortality u systému SKALE. Mezi mortalitou a pohlavím, kolaterálním edémem a lokalizací nádoru nebyla nalezena statisticky významná závislost. Naopak věk, velikost nádoru a skóre Karnofsky před zahájením léčby byly významnými prediktory prognózy. Závěr: Individualizovaná analýza pacientů a zkušenosti neurochirurga nadále zůstávají významnými faktory ve výběru léčby u starších pacientů s diagnózou meningeomu. Nicméně skórovací systémy uplatňované u výběru léčebné modality u pacientů vyššího věku umožňují významně optimalizovat léčebný postup a v konečném důsledku prognózu onemocnění.

Introduction: The incidence of meningiomas increases exponentially after the age of 65. However, this age is characterized by a higher incidence of comorbidities and the benefit of the surgery may not always exceed its risk. Treatment optimization should therefore be objectively assessed using scoring systems as well. Materials and methods: A retrospective analysis evaluated the group of patients treated at the Brno University Hospital between 2013–2018 (N = 108). Patients were older than 65 years of age. Three procedures were considered in the treatment: watch and wait strategy, surgery and stereotactic radiosurgery. The groups of patients were evaluated in terms of the incidence of comorbidities and the outcome of the patients with regard to the choice of treatment modality. Scoring systems were used in the indication for individual types of treatment. Furthermore, short-term and long-term morbidity and mortality were evaluated in individual groups. Results: Significant dependence in the analysis of annual mortality in the SKALE system has been proved. No statistically significant relationship was found between mortality and sex, collateral oedema, and tumour location. In contrast, age, tumour size, and Karnofsky score before treatment were significant predictors of prognosis. Conclusion: Individualized patient analysis and neurosurgeon experience continue to be important factors in treatment selection in elderly patients with a diagnosis of meningioma. However, the scoring systems used to select a treatment modality in elderly patients make it possible to significantly optimize the treatment process and, ultimately, the prognosis of the disease.

• Klíčová slova
• skórovací systémy,
• MeSH
• komorbidita MeSH
• lidé MeSH
• meningeom * chirurgie   MeSH
• pooperační komplikace MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• práce podpořená grantem MeSH