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Small RNA Sequencing Identifies a Six-MicroRNA Signature Enabling Classification of Brain Metastases According to their Origin

I. Roskova, M. Vecera, L. Radova, K. Trachtova, F. Siegl, M. Hermanova, M. Hendrych, L. Kren, V. Vybihal, H. Valekova, P. Kasparova, I. Kolouskova, T. Kazda, O. Slaby, R. Jancalek, J. Sana, M. Smrcka

. 2023 ; 20 (1) : 18-29. [pub] -

Jazyk angličtina Země Řecko

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc23004718

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.

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$a Roskova, Ivana $u Department of Neurosurgery, University Hospital Brno, Brno, Czech Republic $u Faculty of Medicine, Masaryk University, Brno, Czech Republic
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$a Small RNA Sequencing Identifies a Six-MicroRNA Signature Enabling Classification of Brain Metastases According to their Origin / $c I. Roskova, M. Vecera, L. Radova, K. Trachtova, F. Siegl, M. Hermanova, M. Hendrych, L. Kren, V. Vybihal, H. Valekova, P. Kasparova, I. Kolouskova, T. Kazda, O. Slaby, R. Jancalek, J. Sana, M. Smrcka
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$a 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.
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$a Vecera, Marek $u Central European Institute of Technology, Masaryk University, Brno, Czech Republic
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$a Radova, Lenka $u Central European Institute of Technology, Masaryk University, Brno, Czech Republic
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$a Trachtova, Karolina $u Central European Institute of Technology, Masaryk University, Brno, Czech Republic
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$a Siegl, Frantisek $u Central European Institute of Technology, Masaryk University, Brno, Czech Republic
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$a Hermanova, Marketa $u Faculty of Medicine, Masaryk University, Brno, Czech Republic $u First Department of Pathology, St. Anne's University Hospital, Brno, Czech Republic
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$a Hendrych, Michal $u Faculty of Medicine, Masaryk University, Brno, Czech Republic $u First Department of Pathology, St. Anne's University Hospital, Brno, Czech Republic
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$a Kren, Leos $u Department of Pathology, University Hospital Brno, Brno, Czech Republic
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$a Vybihal, Vaclav $u Department of Neurosurgery, University Hospital Brno, Brno, Czech Republic
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$a Valekova, Hana $u Faculty of Medicine, Masaryk University, Brno, Czech Republic $u Department of Neurosurgery, St. Anne's University Hospital, Brno, Czech Republic
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$a Kasparova, Petra $u The Fingerland Department of Pathology, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic
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$a Kolouskova, Ivana $u Faculty of Medicine, Masaryk University, Brno, Czech Republic
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$a Kazda, Tomas $u Faculty of Medicine, Masaryk University, Brno, Czech Republic $u Department of Radiation Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic
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$a Slaby, Ondrej $u Central European Institute of Technology, Masaryk University, Brno, Czech Republic $u Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
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$a Jancalek, Radim $u Faculty of Medicine, Masaryk University, Brno, Czech Republic $u Department of Neurosurgery, St. Anne's University Hospital, Brno, Czech Republic
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$a Sana, Jiri $u Central European Institute of Technology, Masaryk University, Brno, Czech Republic; sana.jiri@gmail.com $u Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic
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$a Smrcka, Martin $u Department of Neurosurgery, University Hospital Brno, Brno, Czech Republic; smrcka.martin@fnbrno.cz $u Faculty of Medicine, Masaryk University, Brno, Czech Republic
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